Melanoma patients got good news today. A 42% drop in the risk of recurrence or death shows that training the immune system on a patient’s own tumor works. The next step is doing that training inside the body. The tumor already carries every antigen the immune system needs, and treating it in place lets the immune system learn from the real thing. Moderna and Merck are already running three phase 3 trials of the vaccine in lung cancer. Lung cancer kills more people than any other cancer, so those trials will show how far this approach can go.

I think people could live 300 years or more. David Sinclair has already reversed the age of mice with reprogramming. That work has since moved to dogs and primates. In our own work we're seeing about three to five years of age reversal for every year of treatment. Supplements like alpha-ketoglutarate, TMG and PQQ slow the aging process. Spermidine and fisetin help kill off older cells. Off-label drugs like tranylcypromine, valproic acid and sodium butyrate switch younger genes back on. Furthermore, I see aging and cancer as very similar diseases. Cancer cells carry many of the same receptors as old cells. The drugs that extend life expectancy also tend to fight cancer. As drugs and protocols that support longevity become more widely available, I believe people who reverse their age will be less likely to get cancer.

[LIVE] Our New Book on Cancer and Why You Need It xitter.cf/i/broadcasts/1AxRnZAvz…

Anktiva is a modified interleukin-15. IL-15 is a signal your immune system uses to wake up natural killer cells and T cells. That is why it works as a cancer drug. BCG is an old bacteria treatment for the bladder. The immune system reacts to it and the tumor gets caught in that reaction. Add IL-15 and you are sending a louder signal to the same cells. We have been injecting interleukins straight into tumors for years. No single cytokine beats cancer alone. You have to change a lot in the immune system at once. A bladder-only approval means most cancer patients still can’t get this drug. Inject it into the tumor and the list of cancers it helps gets a lot longer. Good step. Now expand it.

Bowel cancer in people under 50 has more than doubled in England since 2001. Womb cancer doubled. Kidney doubled. Nobody screens that age group, so screening can't explain it. I've been warning about this for years. Cancer and aging are the same disease. An old cell and a cancer cell send the immune system the same message. Leave me alone. A young immune system ignores that and clears them both out. When 30 year olds are getting the cancers of 70 year olds, their immune system is older than they are. The numbers don't show what I see in clinic. These cancers in young patients are more aggressive. Stage 3 and 4 at diagnosis. Symptoms that kept coming back. Told they were too young. I've had this conversation with the parents of teenagers. The charity says the causes aren't fully understood. Start with the immune system. If you're under 50 and something keeps coming back, demand the test. Too young is not a diagnosis.

A number like 100x deadlier than COVID with no context behind it is how you scare a few million people in an afternoon. So far one lab worker in Siberia has died. Russia is calling it pneumonia and says her tests came back negative for plague. Close to 200 contacts are being watched and none of them have it so far. Nobody outside Russia has verified any of that. That is about all anyone actually knows right now. What is known is that plague is a bacteria, and bacteria respond to antibiotics. The only way you get to a number like that is with no treatment at all. Treated early it is a very different number. I would wait for actual information before sharing anything on this one. A scary number with none of the context does more damage than the facts ever would.

.@DrJesseMorse is very good at what he does. We talked briefly, and he is pushing patients to take control of their own health, which is something I have always cared about. People are already searching for these compounds and buying them. As physicians, our job is to inform and educate. He does that well. Looking forward to Friday.

About 4% of an IV chemo dose actually reaches the tumor. The rest of it goes through the whole body. So patients are buying the entire dose and taking side effects from the 96% that never gets where it was supposed to go.

Everyone tells President Jimmy Carter's case as a Keytruda story. He also had the liver lesion surgically removed and stereotactic radiation to four small spots in his brain before the drug ever got a chance to work. That dropped his tumor burden way down and left dead tumor tissue behind for his immune system to read. One drug got the credit for a combination. Melanoma was also the easiest place for those drugs to work at all. Sun damage gives it one of the highest mutation counts of any common cancer, so the immune system already has plenty to recognize. Give the same drug to a pancreatic tumor and almost nothing happens. The outliers are not a small group either. In CheckMate 067, Opdivo and Yervoy together got median survival to 71.9 months with 43 percent alive at ten years. Metastatic melanoma used to run six or seven months, so that is a huge change. It also means more than half of these patients still need something else. Those patients are the ones I work on. When a tumor is cold you have to build the recognition yourself. Ablate it, inject it, give the immune system a reason to show up.

The FDA approved daraxonrasib for metastatic pancreatic cancer after one prior treatment. KRAS drives about 90% of these tumors. Blocking KRAS slows growth and lifts the immune suppression that KRAS creates, which is the half of the mechanism most people skip. RASolute 302 dosed the drug systemically, and that is where the toxicity came from. We inject KRAS inhibitors into the tumor along with CD40, and we see complete responses in stage IV pancreatic cancer.

Cutting a tumor out throws away the best source of antigen that patient had. That tumor is a catalog of every mutation the cancer carries. Treat it in place and the immune system reads the whole catalog and goes looking for the cells that don't show up on a scan. Send it to pathology in a specimen cup and the immune system never gets to see any of it. You removed the disease and the instructions for finding the rest of it in the same operation. The radical mastectomy era ran on a theory that cancer crept outward like roots, so taking more tissue meant taking more cancer. That theory was wrong, and it took decades of trials to show that taking less didn't cost women a single point of survival. All that extra tissue bought nothing. Surgery isn't free on the immune side either. It ages cells and it suppresses immune function for weeks afterward, and that window is when residual disease has the least resistance it will ever face. So keeping the organ isn't only about how a patient looks or what they can still do with it. Every tumor treated in place is information the immune system gets to keep.

We already use mRNA at the institute. The science here is solid, and delivery is the open question. Putting a vaccine in the arm is not the same as putting it in the tumor. Nathan and I go live today at 1PM PT. Leave your questions below and we will take them on air.

Chemotherapy isn't the villain people make it out to be. The problem is that we hand it to the whole body when the cancer is in one place. Every one of those drugs works by aging cells. Give it systemically and you age everything, including the immune cells you're going to need later. Inject it directly into the tumor and you only age what you meant to hit. There are also patients with too much disease for the immune system to catch up on its own, and in that case you use chemo to knock the burden down fast, then switch over to the immune response once you have room to work. What we're doing now is injecting microdose cisplatin or oxaliplatin into the tumor, which triggers immunogenic cell death, meaning the tumor cells die in a way that recruits and activates immune cells instead of just disappearing quietly. Pulsed electric field ablation speeds that up. Cyclophosphamide into the same tumor drops the myeloid-derived suppressor cells that were letting it hide. Same drugs oncology has used for fifty years to shrink tumors. We're using them to remodel the immune system.

Melanoma has one of the highest mutation loads of any solid tumor, so a neoantigen vaccine has plenty of targets to work with. That is why they started there. Most of the cancers that kill people carry far fewer mutations and shut the immune response down inside the tumor, and a vaccine built on mutations alone has much less to grab onto in those tumors. We inject into the tumor so the immune system gets the whole antigen set and the microenvironment gets activated at the same time. Put the two approaches together and you have something that works outside melanoma.

Pregnancy is an immunosuppressed state by design. Progesterone drives much of it, because the mother's immune system has to stand down or it attacks the fetus. That same suppression removes pressure from anything else the immune system was holding in check, which is one reason certain cancers surface during or shortly after pregnancy. Run the logic backwards and antiprogesterone drugs start to look anticancer, which is exactly what we see. Hormones are immune signals, and oncology still treats them as though they only regulate reproduction.

Prichard Colón was 23 and undefeated when he fought Terrel Williams in 2015. He kept telling the referee about the blows landing on the back of his head. The referee took one point. The fight went on. Those punches land where the spine meets the brainstem, and the skull barely covers that spot. The bleed that started there had nowhere to go. Trapped blood builds pressure. Pressure kills brain tissue. Brain tissue does not come back. Surgeons saved his life that night, but no treatment in medicine could return what the bleed took. He spent 221 days in a coma and the next decade unable to walk or speak, while his parents cared for him around the clock. Prichard did what a fighter is supposed to do. He reported the fouls to the one person who could stop them. It didn't save him. That part has never left me. Boxing learned from him. In 2016 the WBC put a zero tolerance rule on those punches and named it after him. Fighters are safer today because of what he lost. Once brain damage runs this deep, we cannot treat our way out of it. Prevention is the only cure. Rest in peace, Prichard. Praying for his family.