, , ,

PSMA-Targeting Radionuclides:  Serious Side Effects, and Navigating a Safe Course

This new form of treatment for metastatic prostate cancer is being used in Europe, Australia and elsewhere, and being tested in clinical trials in the U.S.  As part of my series on PSMA-targeting, here’s more of the story:

With the dramatic results in some men, why aren’t radionuclides a done deal here in the U.S?  Because – just like the use of magic in fairy tales – they come with a price.

Neil Bander, M.D., Director of Urological Oncology Research at Weill Cornell and a pioneer in the study of PSMA (prostate-specific membrane antigen), developed an antibody that targets this molecule that sits on the surface of prostate cancer cells.  He later characterized PSMA, and found many reasons why it is an excellent way to target prostate cancer.  The alpha particle radioligands (using the small molecule delivery system) target the salivary glands, where a small amount of PSMA is made.  Beta particles such as Lu177, used in the Novartis compound, generally cause only minor salivary gland toxicity, Bander says.  But “since alpha particles are at least 1,000 times more potent than beta particles, when you put the alpha particle on the ligand, it targets the salivary glands and the tear glands, and they get destroyed.”

Now, you might be thinking, losing my salivary glands is a small price to pay for really knocking back and maybe even curing my prostate cancer.  But Bander would suggest that you think very carefully about this.  “When you destroy the salivary glands, the result is absence of saliva, inability to taste, difficulty swallowing, and tooth decay and loss.  Affected patients report that it’s a pretty miserable existence.  So that has proven to be a major impediment to using the small ligands to target the alpha particles.  Despite some amazing responses with the alpha particle, “it can be intolerable for the patient.”

So:  Is there any way to protect the salivary gland?  As it turns out, there is.  “While the small molecule ligand targets the salivary glands and lachrymal glands, antibodies do not,” says Bander.  “Antibodies are much larger molecules than the ligands.”  With the small ligands, the radioisotope “can easily pass through normal tissue barriers.  But when we deliver the radioisotope by use of the antibody, we see no targeting of the salivary or lachrymal glands.”

In fact, “we recently completed a trial at Weill Cornell using our J591 antibody to target the alpha particle, Ac225.  Based on an interim analysis, we have seen minor salivary gland toxicity in six of 27 patients, five of whom previously had been treated with the small ligand.  We found that the antibody-targeted alpha particle was well tolerated and very effective against the prostate cancer, even in patients who previously had progressed after treatment with the ligand Lu177.”  This Phase 1 trial was funded by the Prostate Cancer Foundation.

Another key difference between the antibody and ligand: “The ligand is excreted from the body through the kidney and bladder,” says Bander, and there is a risk of kidney toxicity.  “It has not yet been a significant problem, although there have been a few reports of kidney toxicity from the ligand with an alpha particle on it, and it may take a while to develop.  With the antibody, the path of excretion is through the liver, so the kidney is less likely to be subject to damage from the alpha particle.  The liver is pretty resistant to radiation.”

So… no to the ligands, then?  Not so fast, says Bander.  “Here at Cornell, we have data that suggests the best way to target prostate cancer is actually using a dual-targeted combination of the antibody and the ligand.  Our data show that with the combination, we can deliver a substantially higher dose to the tumor without increasing side effects.”  That’s because these agents each behave differently in the body.  “Dual targeting also allows us to use both the beta and the alpha emitters simultaneously, and our research shows this combination of alpha and beta isotopes to be very complementary.  Ultimately, the dual-targeting approach, with both antibody and small ligand, provides a substantial increase in the dose to the tumor without additive toxicity.  At Cornell, we are beginning to treat mCRPC patients with the ligand-Lu177 plus the antibody-Ac225.  Our laboratory data and our understanding of the biology of how these agents interact suggest a substantial benefit to this dual targeting/dual isotope approach.  The ability to substantially increase the dose to the tumor offers, I think, significant potential benefit for improved survival.”

This is what Bander envisioned 30 years ago, when he first began investigating PSMA.  And, he says, “it’s going to get a lot better.”   At the 2019 ASCO international oncology meeting, a session on PSMA “filled a 4,000-seat auditorium.  I was joking that a few years ago, we could have had that meeting in my hotel room and there would have been room for housekeeping!  It’s just like somebody flipped a switch.  Leveraging the ability to target PSMA for imaging and treatment is in the process of dramatically changing everything about how we approach prostate cancer – how patients are diagnosed, how they’re monitored, and how they’re treated.  If serial PSMA imaging can be shown to reflect tumor response, it has the potential to be used in the development of all prostate cancer drugs going forward to provide rapid insight into drug efficacy.  That will make new drug development in this disease much more rapid and efficient.  It’s a game-changer.  I’m confident that the best is yet to come.”

Note: If you are seeing this as a solo story, click here for more.

 

In addition to the book, I have written much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

 

 

/0 Comments/by
, , ,

PSMA-Targeting Radionuclides:  Dramatic Success

This new form of treatment for metastatic prostate cancer is being used in Europe, Australia and elsewhere, and being tested in clinical trials in the U.S.  As part of my series on PSMA-targeting, here’s more of the story:

As we have discussed here, Neil Bander, M.D., Director of Urological Oncology Research at Weill Cornell and a pioneer in the study of PSMA (prostate-specific membrane antigen), developed an antibody that targets this molecule that sits on the surface of prostate cancer cells.  He later characterized PSMA, and found many reasons why it is an excellent way to target prostate cancer.  Results from work by Bander and others generated worldwide interest – particularly in Germany.

Bander made an antibody that targets PSMA, and linked it to a radioisotope called lutetium 177 (Lu 177), a beta emitter.  With colleagues at Weill Cornell and “with a nod from the FDA,” in 2000, Bander began a series of prospectively designed clinical trials that showed “excellent targeting of metastatic prostate cancers wherever the disease was located in the body.  These treatments resulted in PSA d eclines and improvement of pain.”  At the time, however, he notes, the pharmaceutical industry was not interested in radioactive drugs, and the prostate cancer field was more focused on the development of Taxotere chemotherapy.

In Germany around 2013, physicians began using different agents that bind to PSMA: small molecules, called ligands, instead of antibodies.  Some of these had been developed in the U.S. by John Babich, Ph.D., (now at Weill-Cornell), and Martin Pomper, M.D., Ph.D., of Johns Hopkins.  The Germans tested Lu177 as well as a different radioisotope, actinium 225 (Ac225), “which is an alpha emitter,” says Bander.  “Ac225 is several thousand times more potent than Lu 177,” which, again, is a beta-emitting particle.  (I have to be honest here, I don’t fully understand alpha vs. beta particles, but this article might help those who are motivated understand more.)

In Germany, a “compassionate use” program is often used to allow the use of new, previously untested therapies in patients who don’t have much other hope.  This means that, for a patient with a serious illness who has no other medical options and who agrees to take the risk, doctors can try promising – but unproven – treatments outside of a formally designed clinical trial.  “So in Germany, they were able to give these radiolabeled ligands (small-molecule radionuclides) to patients on an ad hoc basis, not as part of a formally designed and specified treatment protocol.  A number of centers in Germany started to make their own radiolabeled ligands.  They started treating patients and started publishing the results, sometimes on just one or two patients, sometimes on small groups, sometimes on large retrospective series of patients,” in various nuclear medicine journals.

“The other thing they did,” Bander continues, “was, they would only treat patients whose cancers showed up well on PSMA-PET scans.  They selected their patients, which helped them achieve high response rates.”  Notably, a report of two patients treated with a PSMA-Ac225 ligand showed spectacular results.  “To say they were dramatic would be an understatement.  These two patients had already had their cancer progress despite treatment of every kind of therapy then available for prostate cancer.   Everyone was blown away by those two cases.”  The “before and after” images showed that widely metastatic cancer had melted away from the pelvis, ribs, spine, liver and brain.  PSAs that were in the hundreds in one man, and thousands in the other, became undetectable.

Those ligands became readily available in Germany, Austria, Australia, India, South Africa, and “other countries that have more liberal regulatory policies than the U.S.,” Bander says.  “It was just an onslaught of publications, all showing excellent results.  That’s what really flipped the switch and got Big Pharma interested; among them, Novartis and Bayer.”

At the June 2021 meeting of the American Society of Clinical Oncology (ASCO), results from the Phase 3 trial of LuPSMA (Lu177), run by Novartis, confirmed a significant delay in tumor progression and improved survival in men with metastatic castrate-resistant prostate cancer.

Note:  If you are seeing this as a solo story, click here for more.

 

In addition to the book, I have written much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

 

/0 Comments/by
, , ,

Backstory: The Road to PSMA-Targeting Radionuclides

This new form of treatment for metastatic prostate cancer is being used in Europe, Australia and elsewhere, and being tested in clinical trials in the U.S.  As part of my series on PSMA-targeting, here’s more of the story:

Neil Bander, M.D., Director of Urological Oncology Research at Weill Cornell and a pioneer in the study of PSMA, saw the potential of targeting PSMA, a molecule that sits on the surface of prostate cancer cells, soon after it was discovered more than 30 years ago.  His research shed light on why PSMA was such a promising target, and in 2000 his team began clinical trials with J591, a PSMA-targeting antibody he made.

“We were interested in two different approaches,” Bander says.  “One was putting a radioactive isotope on the antibody” – a molecular grenade of cancer-killing radiation – “and the other was putting a drug on the antibody.”  This “antibody-drug conjugate” approach was very new; fewer than a handful of drugs were available to attach to antibodies, “and all of them were owned by drug companies.  We didn’t have ready access to those,” so instead, Bander’s team focused on linking a “radioactive payload” to the antibody.

 The other benefit of using a radioactive isotope as a weapon:  it could be seen on imaging!  “Because of the radioactivity, we could see where this antibody-isotope was actually going,” says Bander.

Think of an old movie, where as a B-52 plane travels, it’s superimposed on a map, and an arrow connects Point A – California, let’s say – to Point B – Guam on our plane’s journey – and all points in between.  Bander didn’t have an arrow, but he could plot the progress of the radioactive isotope just the same.  “We could see immediately that the antibody was going right to the tumor cells.  Wherever we saw tumor sites – on the patient’s bone scan, CT scan, or MRI – we could see those sites lighting up after we gave the radioactive antibody.  So right from day one, we knew we were hitting the target!  We knew we were actually delivering the radioactivity to the tumor sites.”

But Bander and colleagues noticed something odd:  the radioactive isotope was also going to other sites where there was no apparent cancer.  They soon realized what was happening:  the PSMA-targeting isotope was finding cancer that was too small to show up on conventional imaging!  “We knew very early on that this could potentially be a very potent imaging modality.”

The Phase One trials were for men with metastatic castrate-resistant prostate cancer (CRPC).  These were men whose cancer had progressed despite all the standard treatments of the day.  In about 10 to 20 percent of participants, “we did not see their tumors light up.”  Is this because their tumors somehow don’t make PSMA?  Bander doesn’t think so.  (Note: Martin Pomper of Johns Hopkins does, and is working on ways to target those non-PSMA-making cells.)  “If you remove prostate cancer, say in surgery or biopsy, and do a test to see if there’s PSMA – and this has been done in many thousands of patients – almost 95 percent are PSMA-positive.”  Nonetheless, in some men, the PSMA-targeting agent does not show up much on imaging.  “In our studies, we found about 15 percent did not image, and another 5 to 10 percent imaged weakly, but we treated all those patients anyway.  We found that if you are PSMA-negative or PSMA-weak, you are significantly less likely to have a good response to the treatment.”  However:  “If your imaging study lit up like a neon sign, you had a very high likelihood of responding.  It was a pretty clear distinction.”

Bander’s group tested two different isotopes and found that lutetium 177 (Lu 177) was the most effective.  “Responses varied, from no response to PSA stabilization to 95-percent decreases in PSA levels that could last many months,” says Bander.  “We also saw that as we increased the dose, the responses got better.”  Other centers reported success in some animal tumor models with breaking up the dose of radiation.  “Instead of giving just one big dose, if you split it up into two or more smaller doses, you could deliver an even higher cumulative dose.  So we did a phase 1 study of fractionated J591-Lu 177, gave higher doses and got better and more durable responses.”

This was 2007.  Why hasn’t this become mainstream therapy?  One big reason:  the pharmaceutical industry is like a freight train.  Once it gets going on a particular track, it picks up steam and generates huge momentum.  Until that happens, however, momentum can be very slow.  Twenty years ago, Bander says, “pharmaceutical companies had no interest in radiopharmaceuticals.”  Instead, their model was for literal shelf life: drugs put into a tablet or capsule and shipped to sit either at a pharmacy or in a patient’s medicine cabinet.  “Making drugs from living cells was a whole new area,” but the industry has evolved to “this greater willingness to make very complicated products.”

PSMA-targeting radioisotopes have reached a crucial tipping point, says Bander.  “When we characterized PSMA – its specificity for prostate cancer, the fact that 95 percent of prostate cancers were PSMA-positive, that cancer internalizes the PSMA-targeting antibody, that it’s upregulated by hormonal therapy, and that it’s a potential target in other types of tumors – interest started to build.  Then when we showed that if we administered a PSMA-targeting agent, we could actually validate in a patient that it was reaching the cancer, it increased even more.”

A big kick in the pants to the world of PSMA-targeting treatment came from striking results achieved overseas, discussed here.

Note: This is one of a series of stories I’ve just written on PSMA-targeting.  If you are seeing this as a solo story, click here for more.

 

In addition to the book, I have written much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

 

 

/0 Comments/by
, , ,

Killing Metastatic Prostate Cancer with PSMA-Targeting Radionuclides

There’s some bright hope on the horizon for men with metastatic prostate cancer:  it’s PSMA-targeting therapy. This is different from PSMA-targeted imaging, which shows where small bits of prostate cancer are hiding in the body.  But it uses the very same building blocks.  Think of molecular LEGOS:  Instead of attaching the tracer molecule that can “see” prostate cancer, a different isotope (chemical brick), called a radionuclide, can be attached: one that can kill cancer.

PSMA stands for prostate-specific membrane antigen (PSMA), a protein that sits on the surface of 95 percent of prostate cancer cells.  Briefly, to recap the PSMA story so far, we have talked about how PSMA-targeting came to be, covered the first PSMA-imaging agent to get limited FDA approval, and the second imaging agent, which will be used more widely.  Now it’s time to talk about radionuclides.

“With the same chemical scaffold serving as both a diagnostic and therapeutic agent, the field of ‘theranostics’ has recently gained traction,” Martin G. Pomper, M.D, Ph.D., Director of Nuclear Medicine and Molecular Imaging at Johns Hopkins, told me in a recent interview.  Pomper’s team developed the small molecule PSMA tracer that is now the FDA-approved agent, PYLARIFY.  “Recent advances have really lit this form of treatment on fire.”

In Europe and Australia, and in international clinical trials, PSMA-targeting radionuclides such as 177Lu-PSMA-617 (called lutetium-177-PSMA-617, or LuPSMA), are being used to kill metastatic prostate cancer.  “In Australia, 177Lu-PSMA-617  proved superior to cabazitaxel in terms of PSA response and lack of significant adverse effects when compared head-to-head in the TheraP trial,” says Pomper.  “We are working with Novartis on a similar agent, called 177Lu-PSMA-R2, which has even fewer side effects, including lack of uptake in salivary and lachrymal glands.  We are hoping that agents using this molecular scaffold will be able to be outfitted with a variety of even more potent radionuclides than 177Lu.  It is anticipated that 177Lu-PSMA-617 will be FDA-approved at the end of this calendar year.”

In the international Phase 3 VISION trial, reported in June 2021, 831 men with PSMA-positive cancer (cancer that shows up on PSMA-PET) were randomly assigned either to receive LuPSMA plus standard of care, or standard of care alone.  Men who received LuPSMA were about 40 percent less likely to die and 60 percent less likely to have disease progression on scans, compared to the men who received standard of care alone.  After 21 months, cancer progression was delayed for longer: 8.7 months vs. 3.4 months among controls, and men in the LuPSMA group had better median overall survival: 15.3 months compared to 11.3 months in the control group.  Side effects of LuPSMA included fatigue, bone marrow suppression, dry mouth, and nausea/vomiting.

Note:  The TheraP trial compared LuPSMA to chemotherapy (cabazitaxel), but the VISION study did not include chemotherapy, immunotherapy, or other therapies that oncologists would otherwise try.  Oncologists will tell you that  any one therapy may not ever become the magic weapon for beating metastatic prostate cancer – but along with other weapons, PSMA-targeting radionuclides will be part of a pretty impressive arsenal.  Also, as LuPSMA and similar agents get FDA approval, you can bet that doctors will start giving them to patients at earlier stages, when cancer is more vulnerable and easier to kill, and that’s going to boost survival, too.

You might also be wondering about the cancer cells that don’t make PSMA.  New methods of treating them are on the horizon, too.  Pomper is developing new molecules and therapies to target “PSMA-invisible” forms of prostate cancer.  “We are working on agents that work through different mechanisms and can complement the PSMA-targeted agents,” he says.  “I believe that combining theranostics with immunotherapy, PARP inhibitors and other emerging agents – in addition to further optimization of dosage, dose rate and type of isotope of the PSMA-targeting agents – will be able to stave off progression of the disease for years, and that these patients will eventually succumb to ailments other than their prostate cancer.”  In other words, that one day, maybe not too far away, these new forms of therapy will allow men to die with, and not of, prostate cancer.

There are even wider implications, too:  “It took a long time, but now we’re seeing many exciting offshoots of our work in other forms of cancer, as well.  Some pretty amazing things are happening.”

We’re not done here.  I’ve got a lot more on PSMA-targeting therapy.  I want to put it in context, and also break it up into reasonably-sized chunks.  So bear with me: I’m doing this as a series, but to get it to you ASAP, I will post it all at once. Note:  If you are seeing this as a solo story, click here for more.

 

In addition to the book, I have written much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

/0 Comments/by
, , , , ,

Matters of Prostate Cancer Survivorship

Who’s a survivor?  You are, if you are trying to get your life back after a diagnosis of prostate cancer.

 

            Survivor.  What does that word bring to mind?  (Besides, of course, the name of the rock band whose song, “Eye of the Tiger,” went double-platinum in 1982 and was the theme of “Rocky III.”)

            There are more prostate cancer survivors now than ever before.  More men are being cured of localized disease, and more men are living longer with advanced cancer than ever before.  This is great news!  It also means that, as men live longer after treatment for prostate cancer, they have new things to deal with – which brings us to the evolving area of cancer survivorship.

             Survivorship is basically the day-to-day effort to live your best life during or after treatment for localized cancer, or between and in the midst of treatments for more complicated disease.  It’s such a big part of cancer treatment now, in fact, that medical centers are devoting significant resources to it.  One of them is Dana Farber, where medical oncologist Alicia Morgans, M.D., will soon become the new Medical Director of Cancer Survivorship.

The criteria for survivorship used to be a lot more strict, she notes.  “The old-fashioned definition would say that patients living with cancer are not survivors” – that a true survivor could only be someone whose cancer has been cured.  That has changed.  “Now, anybody living after a diagnosis of cancer is a survivor and deserves to have the best quality of life possible.”

Good news: for many men recovering from treatment or living with prostate cancer, help is available.  But it may be up to you to ask for it, if your doctor doesn’t address it specifically.

Note:  Here is where your spouse, partner, family or friends can help.  Those who love you may be aware of some things that you might not have noticed, and their insights can help your doctor take better care of you – if you say it’s okay for them to talk about it.

“Men are stoic, and may not feel comfortable admitting a weakness or vulnerability, or they may not have the words to describe what they’re going through,” says Morgans.  “Or, they may not perceive a problem, but their caregivers or loved ones may.  Raising their concerns – with the permission of the patient – to the doctor can be very helpful.”  This is especially true, she adds, in cases where the patient is experiencing “psychological distress, depression, anxiety, and may not recognize it.  Sometimes the caregiver can say, ‘You don’t realize it, but you’ve had a really short temper.’ Or, ‘You may not recognize it, but you’re sleeping all day, and you’re not eating.’Or, ‘Your cancer is controlled, but your behavior is very different, and you seem really down.’  We may not perceive these changes as being different or outside our norm, but if they’re empowered to speak (with your permission!), your caregiver or family members can really help reflect back to us more accurately what’s happening with you.”

While visiting the doctor, phone a friend!  If it’s not possible for a family member to be there at the appointment, no problem!  “We can often call or conference a loved one in,” with Zoom, FaceTime, or through the medical center.  There are also “electronic ways,” Morgans adds, for loved ones to communicate with the doctor.  You can write an email to the doctor, using the patient’s portal – or even your own.  “In many systems, caregivers can have an account that’s connected to the patient.  I have many patients whose spouse has an adjacent account.  Others just use the patient’s account.”

Be sure to identify yourself, that this is the patient’s daughter, spouse, or friend.  “Don’t represent yourself as the patient if you’re not the patient.”  This does happen, Morgans says.  “Sometimes wives will get on there as the patient, and you know it’s the wife: women tend to talk a lot more than men!  I’ll see a long description, and write back, ‘Is this John’s wife?’”  The information is still appreciated, she adds.

“If there’s something they think the doctor needs to know, and if they’re empowered by the patient to speak to us, the caregiver or spouse can intervene in a meaningful way.”

Sexual Health

Sexual health is “one of the most underrecognized issues” for prostate cancer patients and their partners.  One big reason why is that men just don’t want to talk about it, either because they keep hoping it will get better, or they just decide to be stoic and carry on.  “Even though we have a roadmap for how to address these issues after surgery or radiation, we often lack the support system,” says Morgans.  “There are way too few sexual health counselors specifically dedicated to helping men recovering from prostate cancer.”  And yet: “This is an area of high interest to many patients.  Sexual health affects their personal experience, their mood, energy, everything they do.”  It also affects the health of their partners.

Although this is the issue many men wish would just go away, what they need to do is just the opposite of hoping for the best:  be proactive.  If you had surgery and you haven’t already had this discussion with your urologist, find out what you can do for penile rehabilitation.  This may include pills such as Viagra, Cialis, or other PDE5 inhibitors; vacuum devices for stretching the penis to protect against scar tissue formation; in-office or at-home treatment with a small TENS unit to stimulate nerve regeneration and help with return of urinary control; penile injection; or a penile implant.

Don’t suffer in silence!  Don’t listen to anyone, yourself included, who thinks, “Your cancer has been cured. Just be happy with that.”  There are many steps you can take to recover your sexual health – but they won’t happen if you don’t ask for help.

Intimacy: This is not the same as sexual health, but men on ADT and their partners still need intimacy.  If your oncologist or medical center does not provide counseling in this area, ask for a referral to a sexual health counselor, and keep this in mind: you are not alone, whether you’re the patient or his partner.  There are thousands of couples dealing with this issue, as well.  Your doctor also may be able to recommend support groups, online and affiliated with local medical centers.

Fighting Back on ADT

ADT will try to affect your overall health, but here’s the good news:  you can fight back, Morgans.  Arm yourself with what it might do, and you will be better able to protect yourself against its tactics.  So here, in no particular order, are some of the things ADT might affect, and countermeasures you can take:

Bone health:  Prostate cancer can affect your bones, and so can ADT, in different ways.  Treating prostate cancer in the bones not only protects them, it can improve survival!  ADT raises your risk of osteoporosis – but not only is this treatable, it’s not a “done deal” that every man on ADT will develop it!  “Avoiding fractures is so important,” says Morgans.  “Men who have fragility fractures (due to osteoporosis) can lose their mobility and independence, and can have some major changes in their lives until those fractures are repaired.  If we simply follow the guidelines we already have on how to care for bone and prevent osteoporosis, we can improve those outcomes pretty dramatically.

“A lot of the complications associated with ADT are absolutely things that we can address head on, try to prevent and to reverse; for instance, we have effective therapies to counteract bone thinning and lower the risk of fracture and complications from weak bones.  Many of the known side effects of ADT are not necessarily inevitable.”

Your risk of cardiovascular disease:  Here’s some good news:  A new drug, Orgovyx (relugolix), was approved in December 2020 by the FDA for men with advanced prostate cancer, based on results of the Phase 3 HERO study.  It lowers testosterone, but it works in a different way.  It’s also administered differently – a once-daily pill instead of a shot – and it has a significantly lower risk of major adverse cardiovascular events compared to Lupron (leuprolide).  If you have cardiovascular risk factors, such as high blood pressure, high cholesterol, a family history of cardiovascular disease, diabetes or pre-diabetes, if you’re overweight or if you smoke: heart disease needs to be on your radar, because ADT can make it worse. “Multiple studies have shown that men who have cardiovascular risk factors, particularly if they are not addressed, have higher rates of complications and even death on ADT,” says Morgans.  But treating these risk factors with diet, exercise, and medication if needed, can “improve overall survival and also quality of life.  When your body is healthier, you feel better.”

Note:  For just about every category on this list, exercise is one of the answers.  Men on ADT who exercise lower their risk of having cardiovascular and cognitive effects, developing insulin resistance, diabetes or pre-diabetes, obesity, and high blood pressure.  “All of these are modifiable risk factors,” says Morgans.

Depression:  “Depression is highly treatable,” says Morgans.  “This is important, because evidence suggests that men treated with ADT do have higher rates of depression than men who have prostate cancer but are not receiving ADT.”  But depression is underdiagnosed and undertreated in men on ADT, she adds, “perhaps because of reticence to ask for help, or a perceived stigma with mental illness,” or perhaps because it has crept up, and the patient hasn’t recognized that there’s a problem.  This is where friends, family and caregivers can help.  Depression can affect sleep, appetite, and memory, as well.

Cognitive changes:  ADT can cause cognitive decline and dementia.  However, this is more complicated than it sounds, Morgans notes.  For one thing, symptoms of depression can be mistaken for cognitive decline, and can improve with antidepressants and exercise.  For another, there are multiple forms of dementia, including vascular dementia.  “If that risk is increased because of ADT, then a medicine that reduces the risk of major adverse vascular events could feasibly lower the risk of dementia, as well,” although this remains to be proven in large-scale studies. In general, “what’s good for the heart is good for the brain,” and taking steps to improve your cardiovascular health will help protect your cognitive function, too.  “We also have strategies and mental tricks to help improve memory, and even medicines that may slow the progress of Alzheimer’s.”  The key is to tell your doctor, and get further evaluation and help if needed.  “The choice of therapies may help, as well,” Morgans notes. “In multiple ongoing studies, some really interesting MRI data suggests that there may be differences in some distribution of blood flow in the brain” between androgen-targeted medicines, “including one study with darolutamide that has just launched.”

Hot flashes:  “At its basic level, ADT is lowering testosterone, which keeps men’s bodies functioning in a way they’re used to,” says Morgans.  “Just as we see when women go through menopause, there are widespread changes.  The constellation of symptoms is much broader than just the effects of ADT on the prostate cancer cells themselves.”

Among the most annoying and persistent – and undertreated – are hot flashes, which “can affect mood, sleep, and cognition,” says Morgans.  A novel approach on the horizon is a “wearable,” she adds.  It’s like an Apple watch, and can be linked to your phone.  The basic idea is to stimulate the autonomic nerves on the wrist, with a cool sensation.  “PCF is actively engaged in supporting work that can potentially improve quality of life and reduce hot flashes in men on ADT.  This is an area with much room for improvement, where attention is needed, and pharmacologic therapies aren’t as effective as we wish.”

For now, treatment with antidepressants may help; so can exercise.  Many men seek relief of symptoms with holistic treatments, including relaxation therapy, hypnosis, cognitive-behavioral therapy, and acupuncture.

In addition to the book, I have written much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

/0 Comments/by
, , ,

Enough Dismay! Rewriting the Prostate Cancer Story for Black Men

Just hear me out here.   Look:  I get it.  I come from a high-risk prostate cancer family, with five beloved men, including my husband, my dad, his dad, his grandfather, and my grandfather affected so far.  So you know I am not ever going to downplay the risk.  But enough!  Let’s stop being afraid of prostate cancer, or feeling that it’s just inevitable, or that there’s nothing you can do, or worse, pretending like the risk isn’t there.  Dismay doesn’t help; action does!

*********

 

Why do I worry so much about black men and prostate cancer?  Well, I’ve met a lot of men with prostate cancer over the years, and two who hold permanent places in my heart are both black, both U.S. Veterans, the toughest guys you could ever meet (one, Les, was a USMC drill sergeant!), both devout in their faith, both devoted family men, both not screened for prostate cancer when they needed to be, starting at age 40.  Both were diagnosed with metastatic prostate cancer, and for both, cancer proved an enemy they couldn’t beat.  Their deaths devastated me.  Which is why you may think I’m crazy when I say this now:  Enough with the Dismay!  

Just hear me out.  Look:  I get it.  I come from a high-risk prostate cancer family, with five beloved men, including my husband, my dad, his dad, his grandfather, and my grandfather affected so far.  Two of them, my husband and my dad, got screened, were diagnosed early, and their cancer was cured.  I worry about our two sons, and you can believe I will be on them like the proverbial duck on a June bug to make sure they get screened!  So you know I am not ever going to downplay the risk.  But enough!  Let’s stop being afraid of prostate cancer, or feeling that it’s just inevitable, or that there’s nothing you can do, or worse, pretending like the risk isn’t there.  

Dismay doesn’t help; action does!  Yes, if you are of African descent, you are at higher risk of getting prostate cancer.  However, says physician-scientist Kosj Yamoah, M.D., Ph.D., radiation oncologist and cancer epidemiologist at Moffitt Cancer Center in Tampa, Florida, who is also black, this news should not make you feel defeated. Instead, use this knowledge as advance warning!  Here, then, are some facts and encouraging advice about how you can take action:

Fact: If you’re a black man, you are more likely to get prostate cancer.  Your odds are one out of six, as opposed to one out of eight for men of other races. “In other words,” says Yamoah, “you are 74 percent more likely to get the disease than non-black men.”

How can you act on this?  “Get your first PSA by age 40.”  Note: you might have to ask your doctor for this, because many doctors don’t start prostate cancer screening until patients are in their mid-forties or even early fifties.  But research currently under way at Moffitt and elsewhere  suggests that for some black men, the early fifties may be too late to catch cancer while it is still confined to the prostate.  For whatever reasons – genetic, environmental, or both – in black men, cancer can take less time to develop, and to spread outside the prostate.  So, if you are in your forties and have not been screened, Yamoah advises, ask your doctor for a PSA test and physical exam to check for prostate cancer.  “This is something you can do.  Make it happen.” 

Fact:  Treatments for localized prostate cancer work equally well in men of all races.  But that’s a limited-time offer; it only holds true if cancer is caught and treated early.  “If you or a loved one are African American and have prostate cancer, get treatment in a timely manner!” says Yamoah.  “Particularly for localized prostate cancer, whether you get surgery or radiation, if you are diagnosed and are treated adequately, know that African American men survive the disease exactly the same as non-black men – as long as these two caveats are met.  In equal-access environments, there is no difference in survival.”  However – perhaps because they may be younger, and otherwise may be feeling strong and healthy – if men delay treatment, because “I feel fine,” their cancer may become much more difficult to cure.  Ladies, if you are reading these words, know that you may have to do what my mom and I did with my dad, and what I did with my husband:  make him get regular screening.

Fact:  Unfortunately, treatment is variable.  Success of prostate cancer treatment is operator-dependent; so is quality of life. 

What does this mean for you?  “Seek the best care; don’t settle for less,” says Yamoah.  “It may require a bit of researching, but it makes a difference.”  Making the effort now to do your due diligence and find the best surgeon or radiation oncologist will pay off for years to come.  “In many states across the U.S., we have the best of the best in cancer care, but sometimes patients don’t seek the best care from centers with the appropriate expertise.”  Important note:  “It is also okay to get a second opinion if you are unsure about your treatment plan.”  Unfortunately, patient support groups and online chat rooms abound in stories of regret, anger, or sadness from patients who did not receive excellent care.  Yamoah tells his patients: “Look at it this way.  You would not want to take your car to a bad mechanic; you want to take your car to the best shop.  Why not your body?  It should be no different for health care.  We should be looking for the best.  Being your own advocate for getting the best care could change your life.”

That said, “Don’t fear treatment.”  For every possible side effect you might have, there are effective treatments.  You can get your life back.  The main thing is to be cancer-free.  Also, there are exciting new treatments being investigated now that don’t involve removing or treating the whole prostate; because of advances in imaging (MRI and PSMA-PET), it is now possible to get a pretty accurate idea of the extent of cancer.  On the horizon are treatments that may be able to cure prostate cancer when it is caught very early that have few to no side effects!  

You Need Personalized Care!

      Not only does prostate cancer tend to start at a younger age, and to be more aggressive, in some black men: it also tends to start in a different part of the prostate!  And not only is it often in a different part (the anterior region of the prostate, behind the urethra): it’s a part that’s more difficult to reach, and easier to miss, with a tiny biopsy needle.

What can you do about this?  Yamoah offers this advice: “An MRI and perhaps an additional blood or urine test, to discover or rule out aggressive cancer, will help even the playing field for black men – even for black men who are thought to have lower-risk disease, who may want to be on active surveillance.”  Is it truly safe to be on active surveillance?  Do you truly have low-risk disease – or was there more intermediate- or even high-risk disease hidden in the prostate that was not captured by the biopsy needle?  “Active surveillance works well – as long as patients are staged correctly.”

Here’s another difference:  Black men seem to respond better to some treatments than other men!  Research by Yamoah and colleagues has shown that Provenge (Sipuleucel-T), an immunotherapy drug currently approved for men with metastatic prostate cancer, is more effective in African American men than in other men.  Many black men “seem to have an immune microenvironment enriched for immunosuppressive biomarkers,” says Yamoah.  “Also, in these men, prostate cancer tumors may be a bit more sensitive to radiation.   We are seeing something in clinical trials: that medications like Provenge, and in some instances radiation and ADT, seem to benefit black men more than white men, as measured by longer disease-free intervals and longer survival.”  This suggests, he adds, that “maybe there is some component of a distinct biological subtype that favors certain treatments in black men; it’s a paradigm shift!”

Encouraging results from several studies now under way will help oncologists “tailor treatments appropriately with personalized medicine, based on individual patients’ biology.  This may be leading to a change in the way we see metastatic disease, that will convert it into a chronic disease.  This is all emerging; it’s all new stuff.”

What You Can Learn from Eastern European Jewish Women

“It might seem racist to say that cancer is different in black men than it is in other men,” says Yamoah.  “But that couldn’t be further from the truth: it’s not about race.  It’s about subtypes of cancer.  It is incorrect to say that you have a different type of cancer because of your skin color; the message is that, in order to treat all men equitably, we have to study all populations.”

What are subtypes?  They are specific varieties of a disease – based on differences in mutated genes, or differences in the immune system, or maybe even differences in the microbiome.  Each subtype may respond slightly differently to treatments and also to biomarker tests.  “We know that the cookie-cutter approach, treating all patients the same, does not work with prostate cancer,” says Yamoah.  “So, we need to fine-tune our diagnosis and treatment.”  Unfortunately, much of what scientists have learned about prostate cancer has come from studying predominantly white patient populations.  “We have not had enough African American participation in studies and in scientific exploration.”

How can you help change this?  “Get involved in research.  Become active participants in discoveries for treating prostate cancer.”  Particularly, different biomarkers may work better in black men.  “Whether it’s helping to determine the polygenic risk score – are you at risk, or do you have a family member at risk – or whether it’s helping to find out through biomarker discovery what subtype of prostate cancer you have, and how best to treat that, we could really use your help.”  Many academic medical centers have “biobanks,” collections of patients’ blood, biopsy and tissue samples that can be used for research.  If your doctor asks you to participate, consider saying yes.

Consider the case of Ashkenazi Jewish women – descendants of a very small group of about 350 people who lived in Eastern Europe about 700 years ago.  Around one in 40 people with Ashkenazi Jewish ancestry has a mutation in the BRCA gene, which is linked to breast and ovarian cancer, and also other cancers, including prostate cancer.  “Through studying a sub-population, we discovered that gene,” says Yamoah.  But the implications of this gene are widespread:  “Recently, BRCA mutations have been linked to triple-negative breast cancer, which is more predominant among African women.  If we hadn’t studied it in the Ashkenazi population, we never would have identified it.  Now it has become a biomarker,” and scientists have identified a class of drugs – PARP inhibitors – that work well in cancers with this genetic mutation, including prostate cancer.  “It is no different from studying black men.  What we learn from identifying subtypes is going to benefit the globe.”  The message is “not treating you different; it’s treating you right.”

Each of us has a certain predisposition to disease, Yamoah adds.  “For example, some people smoke for 30 years and never get lung cancer.  Others smoke for 10 years and get it.  We all have a different threshold, based on our genetic predisposition.”  Prostate cancer develops because a gene is mutated.  “regardless of how it occurred,” whether through decades of eating a bad diet (environmental factors), or through inheriting a bad gene (direct genetic predisposition).

The idea of “one size fits all” medicine sounds nice and egalitarian, but in reality, one size does not fit all.  Take, for example, tattoos used in radiation oncology to help pinpoint the areas of treatment.  “We had some patients come through, and the technicians called me into the clinic and said, ‘We can’t find the spot; we can’t tell where the tattoo is.’  I said, ‘That’s because the ink in these localization tattoos was developed for the lighter skin and not for the darker skin!”  Yamoah found a company that has developed fluorescent tattoos (which show up on any skin color), to be available for his patients with dark skin.  “We have made a lot of our discoveries in prostate cancer only looking at one patient population,” but that is changing.  “We are now in an era of moving towards more personalized care, regardless of race.”

Another way you can help is to become an advocate.  “If you are a black man and you don’t have prostate cancer, you have a voice.  You have a sphere of influence; use your influence to encourage others to take heed,” to get tested starting at age 40, and to get prompt treatment from the best doctors you can find.  “If you’ve had prostate cancer and you’re a survivor, please be an advocate.  We need your voice.  Whether you have it or whether you don’t, please help change prostate cancer for this population!”

How Diet, Exercise, and Lifestyle Can Help Lower Your Risk of Fatal Prostate Cancer

If you are overweight, if you smoke, are sedentary, or if you eat a high-fat, high-carb, low-vegetable diet, you are doing prostate cancer a favor:  you’re making sure it has a very hospitable environment.

“Cancer is also a chronic disease,” explains Yamoah.  “Men with prostate cancer who also have high blood pressure, hypertension, diabetes, and coronary disease – many American men of all races who are affected by one or more of these conditions – do worse with their prostate cancer.  If your body mass index (BMI) is high, if you have cardiovascular disease or diabetes, these are conditions that can be made worse by androgen deprivation therapy (ADT).  If we have a man who might benefit from ADT, but who has chronic conditions that are detrimental to his overall well-being, we may have to give suboptimal care to decrease the risk of severe side effects because of these co-morbid conditions.”

What can you do about it?  Exercise has so many beneficial effects on men with prostate cancer, that it might as well be considered a medicine.  “The most effective  avenue for combating the side effects of ADT is exercise,” says Yamoah.  Similarly, “if you are being treated for localized cancer, if you follow a few simple guidelines for wellness, you are going to do better, recover sooner, and have fewer side effects.”

Exercise doesn’t necessarily mean vigorous activity.  Just walking is a great start!  You don’t have to pump serious iron, either; even light weights can help strengthen your muscles and protect your bone density.

If you smoke, there’s never been a better time or reason to quit.  Men who quit smoking immediately begin to lower their risk of dying of prostate cancer.  For more, see this discussion.

Look for foods that fight inflammation and that help prevent insulin resistance – both of which can make cancer grow faster.  Caloric restriction – eating fewer calories a day – is also proving to help slow prostate cancer.

“We wish we had medicine to prescribe that had as many beneficial effects as exercise, weight loss, not smoking, and eating an anti-inflammatory diet,” says medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation.  “What’s good for the heart is good for fighting prostate cancer.  What’s good for the blood pressure is good for fighting prostate cancer.  It’s all connected.”

Finally, one easy-to-fix problem that is common in black men is not getting enough Vitamin D.  “Most black men are Vitamin D-deficient,” says Yamoah, “especially in the U.S.”  Just spending time outside in the sunshine may not be enough, he adds.  But good news:  an inexpensive, over-the-counter supplement can restore your body’s Vitamin D levels.  Note:  2000 IU is the recommended safe dose of Vitamin D.  It’s not a case of, “if some is good, mega doses are better,” because you can get too much.  Just stick with 2000 IU per day.  What does vitamin D do?  “It’s like flame retardant on cancer,” says Simons.  “It helps cool the inflammatory environment that cancer loves so well.”

In addition to the book, I have written much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

 

 

 

 

/0 Comments/by
, ,

Envisioning What PSMA-Targeting Can Do

Imagine looking at a very young Ian McKellen, the knighted British actor, and thinking, “Half a century from now, if they ever film the Lord of the Rings trilogy, he could be the best Gandalf ever!”

That kind of vision is rare – but scientist Neil Bander, M.D., has it.  Nearly three decades ago, Bander, now Director of Urological Oncology Research at Weill Cornell, saw the potential of a newly discovered molecule called PSMA to be used in two ways:  for imaging and also for precisely targeted treatment of prostate cancer.  Over the last few years, both aspects of his vision have been coming true – in clinical trials and newly in practice in the U.S., and in practice in Europe, Australia, South Africa and elsewhere – for a growing number of men with prostate cancer.

You’re going to be hearing a lot more about PSMA, a protein that sits on the surface of 95 percent of prostate cancer cells, and about strategies for targeting it.  One of the most promising tactics involves an antibody developed by Bander and colleagues, and it is no exaggeration to say that without funding from the Prostate Cancer Foundation (PCF, which has invested $28 million into PSMA-targeting research over the last nearly 30 years), the antibody wouldn’t be nearly as far along as it is today.   Briefly, here’s how it came to be:

The late 1980s-early 1990s saw the dawn of monoclonal antibodies, lab-developed clones of B cells that make antibodies designed to zero in on one specific target, like molecular homing pigeons.  Scientists studying cancer were using this technology like gangbusters, “trying to find tumor-specific antigens on cancer cells that could be a way to distinguish cancer cells from normal cells at the molecular level,” says Bander.  (An antigen is a foreign substance, like a toxin, bacteria, or cancer; when the body detects it, the immune system makes a very specific antibody to identify and kill this intruder.)  The hope, if they could find a way to target just cancer, and not normal cells, was to develop more precise treatment – unlike systemic chemotherapy, which takes a toll on the rest of the body.

In 1987, a urologist named Gerald Murphy, who directed the Roswell Park Memorial Institute for cancer research and treatment – and who developed the original PSA test –made a monoclonal antibody, called 7E-11. “Not much happened with that antibody until 1993, when a group at Memorial Sloan Kettering Cancer Center, headed by Skip Heston, used Murphy’s antibody as a way to clone the gene for the antigen that was detected by the antibody,” says Bander.  “When they cloned the gene, their analysis indicated that it was very specific for prostate cancer.  They also found it was actually present in the cell membrane of prostate cancer cells,” and called it PSMA, for prostate-specific membrane antigen.

Soon afterward, Bander received PCF funding to develop antibodies that were specific to prostate cancer cells.  He studied 7E-11, and realized that “if you were looking to target PSMA, this antibody had a significant flaw:  it binds to a part of the PSMA protein that is inside the cell membrane, a site that antibodies can’t readily reach.  In fact, the 7E-11 antibody could only bind to dead prostate cancer cells.   But fortunately, PSMA spans the cell membrane; a short region of it is inside the cell, another region traverses the membrane, and the largest part of the molecule is outside the cell.  Because the antibody is administered through the bloodstream, he notes, “the only thing it sees is what’s on the outside of the cell.  We set out to make a series of antibodies to the part of the molecule that’s on the outside.  A few other groups, including Skip Heston’s group, also set out to do the same thing.  We happened to get there first.”

In 1997, Bander and colleagues published in Cancer Research their development of four antibodies, the first antibodies that could stick to the part of PSMA on the outside of the cell, and the first antibodies that could attach to living prostate cancer cells.  Their most promising antibody was called J591.  Over the next few years, “we did a pretty thorough analysis of these antibodies – where they bound on PSMA and how specific they were for prostate cancer cells vs. normal tissues.”  Then, “because our goal from the outset was to develop this into a therapeutic,” they “humanized” it, genetically re-engineering it from a mouse-derived antibody into a sequence that the human body would not see as a foreign protein.

Bander and colleagues also spent years “really trying to understand more about PSMA, how good a target it was.  They learned that PSMA was very highly overexpressed in cancer; that although normal prostate cells are PSMA-positive, prostate cancer cells are PSMA-loaded.  “We also found that as prostate cancer cells get more aggressive and are more likely to kill a patient, they have more and more PSMA on them.  The more dangerous the prostate cancer is, generally speaking, the more PSMA there is.”

And, they found, the amount of PSMA on the cell surface is affected by male hormones (androgens).  In fact, “when you put a patient on hormonal therapy (androgen deprivation therapy, ADT) you actually upregulate the amount of PSMA on the cell surface by five- to ten-fold.”  The result is “enormous amounts of PSMA sitting on the surface of prostate cancer cells.”  So in effect, ADT, the mainstay of treatment for advanced prostate cancer, makes the bullseye on the cancer cell bigger:  on a tiny scale, from the size of a golf ball to that of a three-foot-wide crater!

But wait!  There’s more!  Bander’s team looked at other types of cancers, and found that the blood supply in almost every other type of solid tumor was PSMA-positive!   For example, a kidney tumor itself does not make PSMA – but its blood supply sure does.  In fact, “the blood supply is pretty strongly PSMA-positive.  We were surprised by this,” but the finding was independently noted by the Heston group.  “We did not and still do not understand why that is the case, but this means a PSMA-targeted drug is potentially useful not just in prostate cancer, but in other types of cancer, where the approach could be to basically eliminate the blood supply to the tumor.  We’ve done some clinical trials to show that this is a real possibility.”

One more early finding, something “we didn’t anticipate,” says Bander:  “When you bind the antibody to PSMA on a living prostate cancer cell, that cell swallows the PSMA and whatever’s attached to it!”  Like a fish gulping a fat worm with a hook, the cancer cell takes in the PSMA antibody and the cancer-killing payload.  This discovery, he continues, “opened up the door to develop antibody drug conjugates: you put a very potent drug on the antibody, direct it specifically to the prostate cancer cells, and the prostate cancer cell swallows up the drug, whereas PSMA-negative cells don’t.  This was, in effect, a door opening to developing chemotherapeutic agents that are only taken up by the cancer cells.”

The door keeps opening wider.  “If you look at PubMed today,” says medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of PCF, “there are now 3,707 research papers on PSMA discoveries.  That’s a paradigm-changing impact.”

Coming up soon: we’ve talked all around the subject of killing prostate cancer by targeting PSMA.  Now how, exactly, does that work?

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

/0 Comments/by