A Professor in Israel Found Out Why Treatment Stops Working in Half of All Prostate Cancer Cases
A lab in Rehovot just found the escape route. And how to close it.
There’s a conversation that happens in doctors’ offices around the world, more often than most people realize. A man gets diagnosed with prostate cancer. He starts treatment. The numbers improve. Then one day, they don’t. The doctor tells him the cancer has become resistant. The treatment that was working isn’t working anymore.
This isn’t rare. This is one of the defining challenges of treating prostate cancer, the second most common cancer in men worldwide, with nearly 1.5 million new cases diagnosed every year. And for decades, in roughly half of all cases, nobody could fully explain why the resistance happened, or what to do about it.
Today, a research team led by Professor Yosef Yarden at the Weizmann Institute of Science published a paper that answered the question doctors have been asking for twenty years.
Here’s What the Treatment Is Actually Doing
Prostate tumors are, in most cases, fueled by testosterone. The body produces it naturally. The tumor uses it to grow. So the standard treatment does something logical: it cuts off the fuel supply. Common prostate cancer medications (enzalutamide and abiraterone) attack the testosterone pathway from two different angles. One blocks the switch inside tumor cells that testosterone activates. The other stops the body from producing testosterone in the first place. No fuel, no growth.
For a while, it works beautifully. Then, in many patients, the tumor adapts. It finds another way.
Think of it like this. The treatment installs a lock on the front door of the tumor’s survival. But in roughly half of all prostate cancer patients, there’s a genetic quirk inside the tumor, a fusion of two genes that shouldn’t be joined together, that acts like a key to a hidden back door. When the front door gets locked, the tumor slips out the back. Quietly.
That genetic fusion, known as TMPRSS2-ERG, has been identified since 2005. It’s one of the most studied alterations in prostate cancer. And yet, as Professor Yarden’s paper notes, “tailored therapies targeting the fused gene remain undeveloped.” For twenty years, researchers could see it. They just couldn’t crack what it was doing inside the cell.
Now they have.
The Back Door Runs Through Your Own Stress Hormone
The back door isn’t some exotic cancer pathway. It runs through cortisol, the same stress hormone your body releases when you’re under pressure, stuck in traffic, or facing a deadline. The genetic fusion grabs onto the switch that cortisol activates inside cells and forms a stable bond with it. Testosterone and cortisol normally keep each other in check inside the body. Block one, and the other becomes free to activate. So when treatment shuts down the testosterone pathway, the tumor’s genetic fusion immediately hijacks the cortisol pathway instead.
But it doesn’t just survive. It does something worse.
Once the fusion hijacks the cortisol pathway, it flips on MYC, a gene that drives aggressive cancer growth and is one of the most dangerous switches a tumor can activate. When the genetic fusion throws that switch, the tumor isn’t merely running out the back door. It’s running toward something more dangerous.
“When the drug blocks the main pathway on which the tumor relies,” Professor Yarden explained, “cancer cells with the genetic fusion succeed in activating another pathway that allows them to continue surviving.” And the implications, he said, are dramatic.
95 Real Patients. The Pattern Was There All Along.
This isn’t a hypothesis built in a petri dish. The Weizmann team went into real clinical trial data, biopsy samples from 37 men in one National Cancer Institute (NCI) trial and 58 patients from a second, a combined cohort of 95 people who had been treated with the standard prostate cancer medications. What they found in that real-world data confirmed what their lab work suggested: patients whose tumors carried the genetic fusion responded worse to treatment. The pattern was there. It had been there all along. It just needed someone to look for it.
Then comes the part that nobody expected.
Steroids. Doctors routinely give steroids to men with advanced prostate cancer. They’re not a side treatment or an afterthought. They’re baked into standard protocols, used alongside chemotherapy, used to manage side effects from other drugs. Prednisone, dexamethasone, combinations of both. Steroids are everywhere in advanced prostate cancer care.
But steroids activate the same internal switch the genetic fusion is hijacking.
“We need to be careful about giving steroids to these patients,” Professor Yarden said, “because they activate the cortisol receptor and may be helping the cancer.”
Read that again. A medicine given to prostate cancer patients as part of standard care for decades may, in patients with this specific genetic fusion, be handing the tumor exactly the fuel it needs for its escape route. Because until today, nobody had mapped the mechanism clearly enough to see it.
Close Both Doors. At the Same Time.
So what do you do with a tumor that has two doors?
You close both.
That’s what the research showed. In lab models, including tumors grown from actual patient biopsies, the team tested blocking both pathways simultaneously, the testosterone pathway and the cortisol pathway together. In tumors carrying the genetic fusion, the combination worked. The tumor had no front door and no back door. Nowhere to go.
Here’s the part that matters for what comes next. There’s already a drug approved by the FDA that works by blocking the same cortisol pathway the tumor is hijacking: relacorilant, approved in March for a resistant form of ovarian cancer. It exists. It’s in use. And it’s already being studied in prostate cancer trials. Professor Yarden said plainly: “Now we can try the combined treatment in human patients with this genetic fusion.”
That’s not a distant dream. The drug exists. The mechanism is now understood. The patients who need it most, those whose tumors carry the genetic fusion, can be identified through a standard biopsy.
We’re not declaring a cure. Science doesn’t work in announcements. It works in steps, each one making the next more possible. What happened today in Rehovot is a step that changes the map for roughly half of all prostate cancer patients worldwide.
Thirty-Eight Years at One Lab in Israel. One Answer.
Professor Yosef Yarden joined the Weizmann Institute in 1988. He trained at Genentech in San Francisco and at MIT. He came home. He’s spent nearly four decades studying how cancer grows, how it spreads, and how it outwits the treatments designed to stop it. The Israel Prize committee, awarding him the country’s highest civilian honor in life sciences, called him “among the most important cancer researchers in the world.”
Today’s paper was published in one of the world’s leading cancer research journals, EMBO Molecular Medicine. The team collaborated with the National Cancer Institute in Bethesda, Maryland, with institutions in the Netherlands, Canada, and Germany. More than three dozen researchers working on a problem that doesn’t belong to any one country, because the men sitting in those doctors’ offices are everywhere.
The man who led this work has been asking the same kinds of questions since 1988. Why does cancer do what it does? How does it escape? Where’s the back door?
Today he found one.
A country of nine million people, one of the most besieged on earth, just moved the needle on a disease affecting men in 185 countries. That’s not a coincidence. That’s what this place does.
Built in Israel. For everyone.