#181 - Robert Gatenby, M.D.: Viewing cancer through an evolutionary lens and why this offers a radically different approach to treatment
Robert Gatenby, M.D.: Viewing cancer ... - Advanced Prostate...
Robert Gatenby, M.D.: Viewing cancer through an evolutionary lens and why this offers a radically different approach to treatment
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Scout4answers
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When I failed 'curative' therapy 17 years ago at age 56, there was no Abi or Enza, etc, & men mostly became resistant to Lupron within 18-24 months. What's more, treatment-emergent adaptations were difficult to control.
An obvious starting point was to tackle things that help progression & metastasis: inflammation / coagulation / cholesterol uptake & synthesis / DHT production via the alternative pathway & so on. I also wanted to have a 'good' estradiol:testosterone ratio.
In the back of my mind I knew that I would progress to the point where I needed to cycle between ADT & high-normal testosterone [T].
For a long while I used a 3 month: 3 month ADT:T cycle. It worked well & QoL was good.
In recent years, I have been using a more BAT-like cycle, which has gone through a number of tweaks.
My aim has always been to avoid CRPC, so it was interesting to hear Gatenby talk about a model where the CRPC population might actually be reduced in each cycle. CRPC cells do well when there is no competition, but non-CRPC cells have a competitive advantage over CRPC cells in the absence of ADT. It's something I hadn't considered.
Balsam01 had introduced Gatenby to the group 3 years ago:
healthunlocked.com/advanced...
-Patrick
• in reply topjoshea13
17 years? Patrick ! You are a hero ! 👏🏼👏🏼👏🏼🥳amazing dude!
Was your curative treatment RP or RT?
Hi PatrickVery interested in your response and would like to learn more about your alternating drug protocol and BAT. 17 years with out reaching CRPC is what I am seeking, nice work!
Have you found an MD to assist you or are you doing this on your own?
I have always been lucky with doctors & they have been willing to prescribe things that I thought might have value.
When I started out, I reasoned that dihydrotestosterone [DHT] is generally protective if one has not received ADT. The androgen receptor [AR] is 'wild type; at diagnosis - it is the estrogen receptor situation that is altered initially. A few years later, I learned how DHT is quickly degraded in prostate cells, and that a metabolite, 3β-Adiol, is the natural ligand for the protective beta estrogen receptor [ERβ]. Anyway, I started out with otc androstenedione (subsequently banned) until I found a doctor who would prescribe testosterone [T] patches.
DHT is your friend until it suddenly isn't. When my PSA doubling time began shortening, I had to move to the alternating protocol. My urologist was willing to prescrible Avodart to inhibit DHT.
When Sam Denmeade at Hopkins started publishing his BAT papers, I was naturally interested, but I was enjoying 3 months of T & Denmeade was injecting T only on day 1 of 28. It seemed that BAT was perpetual castration with brief monthly interuptions.
When I began experimenting with BAT, I realized that I was wrong. T cypionate can clear very slowly. Men are "near-castrate" on day 28, but there is no meaningful ADT period before the next injection.
I ran into trouble while on a monthly cycle & had to move to to 2 months. But the aim really is to extend ADT until the PSA is no higher than at the end of the last cycle. Hopefully, in no more than a 3-month cycle.
For BAT, look in:
pubmed.ncbi.nlm.nih.gov/?te...
Best, -Patrick
Thanks Patrick
"DHT is your friend until it suddenly isn't"
An interesting idea... I thought DHT was always best to suppress. How does one know if DHT is being your friend or not, at any given time? Does it make sense for men on ADT to cycle Avodart/Proscar?
The androgen receptor [AR] isn't altered until it has been subjected to androgen deprivation,
DHT was my friend when I was taking testosterone continuously & PSADT was ~24 months.
When I was cycling between T & ADT, it was just a matter of time before I felt that DHT should be blocked.
Most BAT studies have been on heavily-treated men & I think that it might be best to block DHT in such cases. However, Denmeade evidently feels differently:
"Prior treatment with 5-alpha reductase inhibitors (e.g. finasteride or dutasteride) for treatment of benign prostatic hyperplasia (BPH) is permitted, but patients must be off therapy for ≥ 6 months prior to enrolling on study"
Avodart has a long half-life, & 6 months seems a reasonable clear-out period.
-Patrick
You wrote that RP and sRT failed immediately + a PSADT of approx 24 months. Was there any treatment between the two ? The two don't seem consistent without something in between.
I have had a lot of twists & turns over the years. My PSADT after initial treatments was under 6 months. I began using androstenedione (precursor of testosterone _ chrysin to inhibit aromatase & my PSA froze for each of 6 monthly readings (an infinite PSADT). Ny doctor advised me to inject vitamin B12 & the PSA increased in each of the 3 months that I injected. In the 3rd month it went up 20%.
I stopped the B12 & relied on genistein to counter the hypermethylation in PCa cells. The PSADT eventually lengthened to about 2 years. By this time, my doctor had me on Arimidex instead of chrysin, & Androderm T patches when my andro was running out. My T throughout was ~1,000 ng/dL & my estradiol [E2] was ~20 pg/mL. Happy days.
-Patrick
Thanks for the clarification. Recently I started Chrysin inspired from an earlier post of yours. Before this, I was experimenting with Proplis in order to lower my E2 which is stuck to 45-50. It didn't do the trick, so I switched to Chrysin. My tT is 1100-1300, totally endogenous, because I have familial hypercholesterolemia and on top of that take Avodart that makes my internal feedback loop to increase tT in an effort to keep a balance with DHT. My PSADT is around 9 months and my next step will be sRT after a PSMA scan. Do you think that I should add Genistein?
Genistein has a great affinity for ERbeta (rather that ERalpha) & ERbeta opposes growth-promoting ERalpha. At this point, my PCa ERbeta has certainly been replaced by ERalpha, so I don't bother with genistein any more.
Here's an oldie:
healthunlocked.com/advanced...
-Patrick
Thanks for posting. Its no surprise that those two were inclined to mathematics, physics and engineering before settling for medicine. Empiricism is good, but has its limits. To go the extra mile ingenuity should be added into the mix.
Hey Scout! I spent every waking minute after dx on the web doctors and researching this dammed disease and treatments. TMI brother . We can go nutzs thinking we are gone to be that guy to beat apc . I’m her more than six years after that initial yr of hell and imrt double adt . I did the naturalpathic route along side the conventional. I think it gave me an edge( high dose vitamin
C IV’s bi-weekly my first 18 months. Diet and a lot of exercise is what I recommend. Drop all processed goods and sugar .You’re going to do what is best for you . You’ve found the best pc cite. Very soon you ll step into treatments and rid your body of pc . Kept telling yourself this until it’s so , fight hard to
Maintain strength without testosterone. It’s a bitch . But it is life just the same only in a weakened form of our old self.. love yourself and others . Get through this and get back to what you enjoy most . Be well . You’ve got this . We can’t give in. And you’ve got all of us here praying and pulling for your success. Ask any question and those that have been in your exact shoes shall answer you . We can relate while a normal guy can not . Take care . A year from now you’ll be in a better space . 🙏
Scout4answers• in reply to
Thanks for the encouragement Lulu. I am on the path you advocate.I would like to learn more about your experience with Naturopathic medicine.
I am open to all ideas that seem rational.
• in reply toScout4answers
Hey Scout ! My sweet wife insisted on the naturalpathic approach . I have Dr Michael Uzick who is a naturalpathic oncologist in Tucson az. The main thing was diet and nutrition plan . But for the time I had tubes and a foley I did 50 gram vitamin c iv’s bi weekly and sometimes we added dmso I think this helped my urology to drive again after being shut down by pc tumors . Uzick gives c patients vitamin c ivs . It cost then about $150 per Iv. It as no fun sitting for two hrs doing so . My nutrient list now is $600 per month . Half my income on Ssdi .. I take about 30 pills a day . I’m on the test adt drug still stopping adrenal t . And I chopped the boys in 2017 . Psa<1 t=3 for six years now . My problems are no T ,osteopenia and degenerative joint disease . I had two yrs with hard antibiotics for uti s .That took my joints down . Mom has bad arthritis and djd to the max . Dad had pc . Poor guy . I see you taking this bull by the horns . We can’t kill it . It’s part of us now ,but we can kick it in the teeth and ride it down the the old town road . You won’t be able to breath easily until you squash this sob . Your best bet is now in this first round . Hit it hard . Love yourself in the process. We get downgraded physically but we can’t sell our soul to the devil or let anger take over . I did it three years . A total waste . I Wish you luck ? Prayers for mercy my man 🙏. God bless!
Robert Gatenby's knowledge of Physics appears to be rather limited. I am afraid his approach may lead cancer patients down the rabbit hole.
Hi dac500re: Gatenby's knowledge of Physics appears to be rather limited.
This is all new info to me so would you please expand on why you say this .
I have spent my working life teaching physics and doing research in physics. His comment on Newton and Einstein is not very deep.
Does the alternating of therapies as a way to either kill the cancer or at least preventing one from becoming CPRC make any sense to you?
Any adaptive procedure makes more sense to me than "Give the patient the full dose until it stops working". Without feed-back loop stabilization we would still be riding on horses and using smoke signals for messaging.
Ancient Greeks had invented a cylinder-piston mechanism to "magically" open the gates of a temple by lighting a fire outside it which would boil water into steam. The power of steam was known since then. The industrial revolution started at the end 18th century when James Watt invented the centrifugal governor (a feedback mechanism) harnessing the rotational speed of the steam engine. en.wikipedia.org/wiki/Centr...
• in reply toJustfor_
Agreed. Just for , you’re fascinating me with history . I like it ? Started taking a test drug over six years ago . I took six pills per day for about 2and a half yrs. Then I was told some guys only take four and feel less side effects . So I did and felt much better . Now I take 2 per day on most days . Some days none . But I’m just lucky . I feel like tossing them completely but the Docs say no way! I like getting tested tri monthly .Good day!
While you were teaching physics, I was on the throne taking them....
Good Luck, Good Health and Good Humor.
j-o-h-n Tuesday 10/26/2021 7:30 PM DST
This is a very excellent and intelligent podcast conversation about adaptive therapy considerations for cancer treatment in general, and prostate cancer in particular. Well worth the time, especially in the 2nd half.The considerations of NOT staying on continuous ADT even when PSA becomes undetectable, as it very often does, for a while, but taking that as an opportunity to move towards “extinction” of the cancer by adding subsequent therapies, again in sequence, at that time. These may include chemo, angiogenesis inhibitors and immunotherapies .
Also clarifies the adaptive role of alternating ADT with periods of high testosterone in BAT or other cyclic programs such as I and others are doing.
I will continue to follow Peter Attia’s podcasts. Next up: all about testosterone and testosterone replacement.
Thanks for posting.
Glad you found it interesting. I have been following Peter Attia's work on life extension and aging for years, very bright guy. I Would like to learn more about yours and others experience in cycling ( not biking 
) and BAT using different therapies.
Have you found an MD who will support it or have you done it on your own?
As for my experience so far with cyclic high T, here is a summary I sent another member today.
I am doing high T cycles with no ADT. I had severe sarcopenia. My PSA remained detectable but low and fairly stable since pelvic RT of PSMA avid LNs in late 2019. It took me three consults and lots of articles to convince my MO to allow me a trial of modified BAT. My last PSA before starting it was 0.080.
Here is what we know from BAT trials which were more advanced mCRPC than me: some did very well on BAT and some did not. The latter had a prompt and strong rise in PSA with the first cycle. Those individuals were withdrawn from the study and did not appear to have radiographic progression as a result of the one cycle. I find that reassuring.
The ones that did have a favorable response to BAT over multiple cycles (2 weeks with high T, alternating with 2 weeks at castrate T). These also had a very moderate rise in PSA during the high T, but came back down to baseline or even lower when off T.
On that basis I tried 4 weeks of high T (400mg of testosterone cypionate every2 weeks X two doses). Then four weeks with the T gone. I did not do ADT in the off cycles so far, but will add that when needed. I responded very well. After three cycles, now six weeks on and four weeks off, my PSA was 0.09 at the end of the last off cycle.
I chose not to do the 2 weeks on / 2 weeks off per standard BAT because my PC was indolent and slow growing. So my guess is that slower longer cycling will be a better match to the growth cycles. Personally, my natural testosterone does not recover much off ADT, last one was 80. If it did then I would think ADT in some form should be used. (? Enzalutamide per Morgentaler? Vs Firmagon or Orgovix?)
I will continue to follow Peter Attia naw. 👍
Does RT count as a subsequent therapy?
Opening the link, I found the podcast embedded in full near the bottom, Nal.
Sorry I have not but I will work on getting that info.
Interestingly Gatenby’s mini trial was to keep patients on lupron and only give Zytiga intermittently…
For more info about adaptive therapy check out the Center of Excellence for Evolutionary Therapy (at the Moffit Cancer Center) which Gatenby cofounded. Lots of info about adaptive therapy and evolutionary medicine. Now, we need to find oncologists (and health care plans) willing to implement PCa adaptive therapy trials and treatments. Any suggestions?
Thanks Jamfrak I will check it out
For even more in-depth info about adaptive therapy research and trials, and evolutionary medicine, explore the Anderson Lab's website.The Lab is a project of the Moffitt Cancer Center.labpages.moffitt.org/anders...
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