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SUNDAY SCIENCE: HOW AN ‘IMPOSSIBLE’ IDEA LED TO A PANCREATIC
CANCER BREAKTHROUGH  
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Gina Kolata, Rebecca Robbins
May 12, 2026
The New York Times
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_ The new strategy also holds promise for lung and colon tumors.
Here’s how scientists discovered it. _

An experimental drug, daraxonrasib, is the first to substantially
extend the lives of patients with pancreatic cancer in a clinical
trial., Kim Raff for The New York Times

 

Pancreatic cancer is one of the most dire diagnoses in medicine. There
are few available treatments, and they do little to help. For decades,
experimental drugs flopped in trials. Many researchers believed the
biological obstacles could not be surmounted.

In what seems the blink of an eye, all that has changed. A drug
nearing regulatory approval, daraxonrasib, is the first to
substantially extend the lives of patients with pancreatic cancer. It
works by targeting a cellular protein that fuels not just nearly all
pancreatic tumors, but also many lung and colon cancers. Those three
are the leading causes
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Now, 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.

The long scientific journey that led to the drug is a triumph of both
public and private research funding, succeeding only after decades of
false starts and dashed hopes — and the unraveling of conventional
wisdom that turned out to be completely wrong.

“Every time there was an advance, it led to another dumping of dogma
and finding out that what everybody assumed was true was actually not
true,” said Adrienne Cox, a researcher at the University of North
Carolina.

Scientists long ago identified their target: a smooth-surfaced protein
inside cells, called KRAS, that is altered in certain cancers and
drives their growth. Researchers often described it as a “greasy
ball,” seemingly impervious to assault.

“Almost everybody thought that it was going to be impossible to make
drugs against KRAS,” said Marina Pasca di Magliano, a researcher at
the University of Michigan.

But it was possible. Over decades, academics laid the groundwork with
support from the National Institutes of Health and the Howard Hughes
Medical Institute, a nonprofit medical research organization. Then,
industry refined the chemistry and turned the idea into a drug —
using a novel approach that glues molecules together to grab and shut
down KRAS.

A colored scanning electron micrograph of pancreatic cancer cells in
an early stage of the disease.Anne Weston/Francis Crick Institute, via
Science Source

And now that the protein-targeting strategy shows promise, multiple
companies have jumped into the fray. Dozens of similar drugs
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tested for cancers of the pancreas, lung and colon.

The drug that opened the floodgates, daraxonrasib, has been
fast-tracked for review by the Food and Drug Administration and could
win approval later this year. Until then, the agency has signed off on
a plan by Revolution Medicines, the small Silicon Valley company
developing the drug, to offer early access
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to some patients.

The pills, three taken daily, are not a cure — eventually,
daraxonrasib stops working. Many patients do not respond. And it has
side effects that can be harsh, including rash, diarrhea, fatigue,
nausea and raw, split fingertips.

Until now, however, patients with pancreatic cancer have typically
been offered grueling chemotherapy that does little to extend their
lives.

A gland deep in the abdomen, the pancreas helps regulate blood sugar
and digestion. Only 3 percent
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of these patients with cancer that has spread to distant parts of
their body are still alive after five years. The disease kills more
than 50,000
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Americans a year.

Revolution tested daraxonrasib in a late-stage clinical trial in
patients who had metastatic cancer and had already tried chemotherapy.
For these patients, further treatment was viewed as a Hail Mary.

Patients who received the drug lived for a median of over 13 months,
compared with less than seven months for patients who had
chemotherapy, the company said in a news release
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Researchers will present the findings
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cancer conference in Chicago later this month. The study has not yet
been published in a peer-reviewed medical journal.

Scientists say the drug could turn out to be cancer’s equivalent of
breaking the four-minute mile. “It’s the beginning, not the
end,” said Dr. Elizabeth Jaffee, a pancreatic cancer researcher at
Johns Hopkins University.

THE GREASY BALL

Kevan Shokat, a scientist at the University of California, San
Francisco, spent five years screening 500 molecules searching for one
that could wedge itself into a crack in the KRAS protein..Kelsey
McClellan for The New York Times

The usual methods for finding a new treatment were not going to work
for pancreatic cancer.

A typical way for a drug to work is by binding to a pocket on the
surface of a crucial protein, like a rock climber finding a crack in a
cliff face, in order to disable it. But KRAS, the greasy ball, had no
obvious places where a drug could attach.

It was in the early 1980s that researchers at M.I.T. and Harvard
discovered that human cancers could be caused by mutations in a family
of genes called RAS genes. One of them was the KRAS gene.

The KRAS gene helps cells regulate growth. It directs cells to make
proteins that share its name — KRAS proteins — that are switched
on when a cell needs to replicate.

Most of the time the 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.

They failed spectacularly.

“Everyone ran away from KRAS,” said Channing Der, a pioneering
KRAS researcher who is now at the University of North Carolina.
“Very prominent members of the field argued this is lunacy, that
this is crazy.’”

Kevan Shokat, a scientist at the University of California, San
Francisco, was not convinced. 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
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the field, and he later joined Revolution
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as an academic co-founder and adviser.

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.

Greg Verdine of Harvard University worked to design a molecular glue
to disable KRAS. Sophie Park for The New York Times

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.

Then the drug would drift away, moving on to attack another KRAS
protein.

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
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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.” Similar approaches in
animal experiments had killed mice.

“We were nervous about that from the beginning,” said Dr. Mark
Goldsmith, Revolution’s chief executive. “But we started shrinking
tumors in animals, and seeing that the animals seemed to be just
fine.”

In 2022, Revolution was confident enough to start giving tiny doses of
the drug to the first patients in a safety study. “We started seeing
shrinking tumors, and side effects that were manageable,” Dr.
Goldsmith said.

At a medical meeting a few years ago, Dr. Anirban Maitra, now the
director of the Perlmutter Cancer Center at NYU Langone Health,
listened to a presentation of data on patients who got daraxonrasib in
an early clinical trial.

He was stunned that a drug that blocks KRAS in both cancerous and
normal cells wasn’t harming patients by damaging their healthy
tissue.

“How is this possible?” he recalled thinking. “How are these
patients not dying?”

Revolution’s drug had managed to strike a delicate balance,
devastating cancer cells while mostly sparing normal ones.

‘A PRETTY GOOD LIFE’

Rhea Caras of Palos Verdes Estates, Calif., was diagnosed with
metastatic pancreatic cancer in 2023 and told she would most likely
have just months to live. Stella Kalinina for The New York Times

In the fall of 2023, Rhea Caras, a retired lawyer in Palos Verdes
Estates, Calif., got a tip from her oncologist: He would soon be
flying to Europe to attend a medical conference. He was excited about
early data that researchers would be presenting on a promising
experimental drug.

Earlier that year, Ms. Caras had been diagnosed with metastatic
pancreatic cancer and told she most likely had just months to live. By
the time her doctor told her about the experimental drug, she had
already tried a first line of grueling chemotherapy and was looking
for her next treatment.

Ms. Caras soon joined a mid-stage daraxonrasib trial. Over two years
later, she is still taking her pills every day.

Now 67, she routinely deals with side effects like fatigue, nausea and
digestive problems. But her cancer has shrunk. Next month, she plans
to travel to Hawaii with her family.

“I’m pretty sure I would not be alive still but for this drug,”
she said. “I’m living a pretty good life, and I did not expect
that.”

Ms. Caras said she did not know how long the drug would continue to
work for her, but she was now thinking years ahead. “I think I could
die of something else,” she said.

For the scientists who pioneered research into KRAS, the burst of
excitement has been long in the making.

In 1982, Robert Weinberg, a scientist at M.I.T., made one of the
seminal discoveries about how RAS genes fuel some cancers. In an
interview this month, Dr. Weinberg, now 83, marveled that it had taken
44 years for patients to benefit from his work — and that he had
lived long enough to see it.

“It would have been nice if the Good Lord had sent us down something
easier to drug,” he said. “But that turned out not to be the
case.”

GINA KOLATA [[link removed]] reports on
diseases and treatments, how treatments are discovered and tested, and
how they affect people.

REBECCA ROBBINS [[link removed]] is a
Times reporter covering the pharmaceutical industry. She has been
reporting on health and medicine since 2015.

_Subscribe to the NEW YORK TIMES_ [[link removed]]

A PASSION FOR SPECIES
[[link removed]]HUMBERTO
BASILIOSCIENCEHerpetologist Alejandro Arteaga has won accolades for
his efforts to identify and protect Ecuador’s reptiles and
amphibians. But his methods have entangled him in controversyMay 14,
2026

* Science
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* pancreas
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