From Lab to Life: Cancer Cells from ‘On’ to ‘Off’

Consider biological evolution. It made us humans (and the entire amazing planet) what we are today.  It gave us oxygen to breathe, plants to eat and absorb CO₂,  maybe even indirectly the magnetic field to protect us from radiation…

But plants and animals are not the only things evolving.  So are cancer cells.  Viruses. And things that do us harm.

Pancreatic cancer is caused by a ‘greasy ball’ of protein, called by scientists KRAS, which regulates cell division:

“The KRAS protein… acts as a critical molecular “on/off switch” in cells, regulating vital functions like proliferation, differentiation, and survival.  …mutated KRAS becomes permanently active, driving uncontrollable cell growth and tumor development.”

In other words, pancreatic cancer (also lung cancer, colon cancer, and other forms) occurs when mutated cancer cells are turned ‘on’ – and proliferate without stopping, eventually killing us.

Scientists decades ago thought about ways to shut down KRAS with drugs, to turn it permanently to “off.” It turned out to be difficult. KRAS has an Iron Dome outer wall made of fat that protects it against invading drugs.

Writing in the New York Times, Gina Kolata with Rebecca Robbins (May 12, 2026) tell the story of a new drug, daraxonrasib, that turns KRAS cells ‘off’ – permanently.  It doesn’t cure pancreatic cancer. But it prolongs life, at a time when, say, another six months of life can be supremely valuable.  The authors note that “some scientists predict that the approach could wind up being the most significant advance in cancer treatment in 15 years, since the arrival of immunotherapy.”

Most of the time the KRAS protein is in the “off” position. The cancer-causing gene mutations, however, leave KRAS proteins stuck in the “on” state. Once scientists identified the KRAS gene’s role in cancer, there was a surge of activity among drug companies hoping to develop drugs targeting RAS proteins. Most scientists gave up – penetrating the fatty outer wall of KRAS proved impossible.  Scientists just gave up.

Except one.

Here is the story. “Kevan Shokat, a scientist at the University of California, San Francisco, was not convinced [it was impossible]. He had an idea: Maybe the greasy ball wasn’t as smooth and impenetrable as everyone thought.  He spent five years screening 500 molecules, until finally he found a crack in the KRAS protein into which one of his molecules wedged. It didn’t become a drug, but it was the first sign that maybe naysayers were wrong to think the KRAS protein was “undruggable.”  Dr. Shokat published his landmark finding in 2013.”

“…Around the same time, Greg Verdine, a scientist at Harvard, was starting a company that would look for creative ways to target proteins, including KRAS. He wondered if there were any molecules in nature that could get around the myriad challenges of binding to KRAS protein. …Nature, it turned out, had made what he called molecular glues, which can stick together two proteins that would normally never attach to each other. His thought was to custom-design a molecular glue to disable KRAS.  At the company he started called Warp Drive Bio, Dr. Verdine and his team developed a strategy to stick a drug onto another protein in the cell, cyclophilin, and then use the larger combined surface to wrap around KRAS and shut it down.”

“Together, Dr. Shokat and Dr. Verdine’s research showed that the greasy ball could be conquered after all. In 2018, Revolution, a small company that had been focused on drugs to fight infections, acquired Warp Drive and expanded on its work.  Revolution’s chemists took a bold approach to designing a compound, surprising company leaders. Their drug hit KRAS proteins when they were in the “on” state both in healthy and cancerous cells, switching the “on” state to “off.”

There was high risk.  “Similar approaches in animal experiments had killed mice.”  The new drug might kill healthy cells.

But it didn’t. And in experimental trials, those with terminal pancreatic cancer are living for much longer.  No cure – but added months of life are valuable.  Simply – cancer cells divide and proliferate far more and far faster than normal cells. Shut them off!

What did it take to develop daraxonrasib?   Out-of-the-box thinking by a scientist, doubtless cautioned that his quixotic effort could end his career.  Large research budgets for high-risk low-odds projects.  Startups, former and merged.  Persistent dogged scientific curiosity.

Drugs that turn off proliferating metastasizing cancer cells could be a huge breakthrough.  Please stay tuned.

Postscript:  I believe Shokat is the son of former Iranian Jews, who migrated to the US and were active in opposing the current regime in Iran.