The most hopeful cancer news in years: Why a roomful of oncologists gave a standing ovation for a line graph

In a darkened convention hall in Chicago on May 31, a Harvard oncologist named Brian Wolpin stood at a podium and in a voice that sounded as if he was reading from the phone book, recited a set of numbers that brought a roomful of cancer doctors to their feet for 42 seconds. Adam Feuerstein, a biotech correspondent for the health news site Stat who has covered cancer conferences like this for two decades, said he had never witnessed anything like it. The applause lasted so long that Wolpin, caught off-guard, ad-libbed: “That time was not built into my talk.”

What Wolpin had just shown attendees at the American Society of Clinical Oncology’s (ASCO) annual meeting was a simple line graph: a drug called daraxonrasib had nearly doubled median overall survival in a 500-patient trial of a form of previously treated advanced pancreatic cancer. ASCO’s chief medical officer Julie Gralow termed the result not a home run but a “grand slam.” Toronto oncologist Jennifer Knox called it a “game changer.”

Wolpin received such a rapturous response at ASCO because pancreatic cancer is among the most pernicious and treatment-resistant cancers in existence, killing more than 50,000 Americans a year, among them Supreme Court Ruth Bader Ginsburg. The cancer has a five-year survival rate in the low teens.

Wolpin, who began his career in the mid-2000s at the world-class Dana-Farber Cancer Institute, told The Bulwark: “I think I saw several patients that first year of fellowship who had pancreatic cancer, and they all died in like three months. It’s not supposed to happen here, right? You’re supposed to have figured this out.” For decades after President Richard Nixon declared a “war on cancer,” deaths continued to mount and medical progress on many cancers remained all too limited.

But a change is well underway. The US death rate from cancer has fallen 34 percent from its 1991 peak through 2023, and the five-year relative survival for all cancers combined reached 70 percent for people diagnosed between 2015 tto 2021, up from 50 percent in the 1970s. And while daraxonrasib got the standing ovation, it was only the loudest moment in a week — and a decade — of steady, compounding victories over cancer.

One major driver of the shift is immunotherapy. Rather than attacking a tumor directly as conventional chemotherapy does, these treatments use a patient’s own immune system to hunt and kill cancer cells. You can see immunotherapy’s powerful effects through the story of former President Jimmy Carter, who was diagnosed in 2015 at age 90 with metastatic melanoma that had spread to his liver and brain. That should have been a sign for newspaper editors to update their planned obituaries immediately; yet after being treated with the immunotherapy drug pembrolizumab, as well as surgery and radiation, Carter watched his tumors vanish and managed to live another decade.

And scientists keep pushing the frontier further. Moderna and Merck reported that the combination of a personalized mRNA vaccine — the technology behind the Covid shots, retrained on each patient’s own tumor — and an immuontherapy drug (pembrolizumab) reduced the risk of recurrence or death for high-risk melanoma by 49 percent after five years. In a small, early Memorial Sloan Kettering trial of a similar vaccine appeared to help some pancreatic cancer patients stay cancer-free longer after surgery. Seven of the eight patients who responded to the vaccine were still alive four to six years later, with a larger trial now underway.

A Memorial Sloan Kettering trial of a similar vaccine in 2024 kept pancreatic cancer at bay in patients whose immune systems responded to it. And for blood cancers, a single infusion of reengineered immune cells — called CAR T-cell therapy — has begun producing something that looks close to a cure: Emily Whitehead, the first child with cancer ever treated with CAR T, is now more than a decade cancer-free and attending college. (I wrote in more detail about immunotherapy and CAR T last year.)

And scientists’ ambitions are growing, from treating cancer to stopping it before it starts. Last week, a team led by the Francis Crick Institute’s Charles Swanton reported that a blood test measuring 14 proteins, combined with basic risk factors like age, smoking, and lung disease, could help identify people likely to develop lung cancer years before diagnosis. They also found an intriguing clue from an older drug trial: An anti-inflammatory drug seemed to cut lung cancer risk nearly in half among people with the highest inflammation levels.

This is still early evidence — not yet a blood test and prevention treatment doctors can offer patients — but Swanton compared it to how statins work for heart disease. Just as cholesterol tests can predict a person’s risk of heart disease, and then statins can be given to lower cholesterol, the protein test identifies lung cancer risk and the anti-inflammatory drug reduces it.

And no story on modern medical miracles would be complete without an appearance from GLP-1 drugs, which truly do seem to do everything. A University of Pennsylvania study of more than 110,000 women, also reported at the ASCO meeting this week, found that taking GLP-1 drugs like Ozempic was associated with about 30 percent lower breast cancer incidence.

Both findings are early, so we shouldn’t expect major changes overnight. It took decades between the development of a test for LDL cholesterol levels, the introduction of statins, and the undeniable proof of heart disease prevention. But oncology is clearly moving toward catching cancer before it takes hold, just as we have with heart attacks.

Medical advances come with a literal cost. The new medicines are brutally expensive, with the average monthly price of a new cancer drug more than doubling between 2009 and 2019, while about half of surveyed American cancer patients and survivors have to take on debt to pay for treatment.

Many of those high prices will eventually fall, once patents run out and generic versions emerge. But a greater worry is that the scientific engine driving these advances is being throttled. Almost every advance I’ve mentioned can be traced back to federally funded basic research, which the Trump administration has been attacking relentlessly.

In 2025, the administration froze or canceled thousands of National Institutes of Health (NIH) and National Science Foundation (NSF) grants, while new NIH awards fell by billions of dollars. Congress later rejected the deepest proposed NIH cuts, but the damage was already real: Hundreds of NIH-funded clinical trials were disrupted, and early-career scientists became much less likely to win major grants. In saving dollars with those cuts, we risk losing discoveries that would save lives, at the very moment when cancer research is paying off.

The cost of those lives was made visceral at the ASCO meeting. In the opening address, ASCO’s outgoing president Eric Small spoke about his partner, Amy Lin, a University of San Francisco San Francisco oncologist. Lin had died in December of metastatic clear cell ovarian cancer, a deadly disease that still has few treatment options. He brought on the grief expert and author David Kessler to give a talk on compassionate end-of-life care.

Perhaps more than any other medical specialty, grief and loss have always been an inseparable, if rarely discussed, part of oncology. Brian Wolpin started his career watching pancreatic patients die within months and feeling certain it wasn’t supposed to happen at a place like Dana-Farber. The ovation he got was the sound of a room realizing he might be right — that the disease that once seemed untreatable is starting to lose its terrible power.

I would allow Federal PPACA exchanges to offer Interstate Class Drug Plans,
exempt from state control that cover under contract at the time of policy issue at least:
1. 80% of all FDA-approved recombinant drugs by key active entity
2. 80% of all key FDA breakthrough chemical active entities under patent as of January 1 of the coverage year
used in a drug approved by the FDA by August 1 prior
3. 80% of all key chemical active entities under patent as of January 1 of the coverage year
used in a drug approved by the FDA by August 1 prior
4. 90% of all WHO “essential” drugs

Interstate Class Drug Plans that don’t meet all those minimums could be sold off the exchanges.

This system would allow for genuine negotiation between drug plans and drug companies. Drug plans would have an incentive to try to buy drugs from drug companies and drug companies would have an incentive to make deals to make sales.

Plan formulary drugs would be supplied on an all-the-doctors prescribe basis. The co-pays on plan formulary drugs would be roughly equal to mere manufacturing cost.

Non-formulary drugs might be covered by timed vouchers with plan-set amounts ($700 plan pay, 30-day supply, TV_Drug_32, to be dispensed by plan-listed pharmacy in June 2026). Voucher plans would not have fixed premiums.

Voucher issuance would require individual approval by a plan (or third party) reviewer. The prescriber would normally have to fill out an online request questionnaire.

Daraxonrasib (RMC-6236) is a RAS inhibitor drug. It is undergoing testing by Revolution Medicines to treat advanced solid tumors with RAS mutations, especially metastatic pancreatic ductal adenocarcinoma (PDAC) containing KRAS G12X mutations. It received a breakthrough therapy designation from the US FDA in 2025.

Daraxonrasib is an orally active and multi-selective RAS inhibitor. It uses a tri-complex mechanism to target the active, GTP-bound form of RAS proteins, including mutant and wild-type forms. Unlike conventional RAS inhibitors, it first binds to the chaperone-like protein cyclophilin A to form a complex, which then attaches to active RAS. This interaction blocks downstream effector binding and inhibits oncogenic signaling.

In 2026, daraxonrasib completed a phase 3 clinical trial (RASolute 302) to assess efficacy compared to standard-of-care chemotherapy. The trial met all primary and key secondary endpoints, including progression-free survival (PFS). The company reported median survival of 13.2 months with daraxonrasib vs. 6.7 months with standard chemotherapy. The hazard ratio for death was 0.40 (a 60% reduction in risk of death; p < 0.0001). Daraxonrasib was generally well tolerated. Its side effects include rash, diarrhea, fatigue, nausea and raw, split fingertips. The safety profile is manageable with no new safety signals. Although the trial was randomized, it was open-label (not blinded), and both the patient and outcome assessors knew if a patient was administered Daraxonrasib.

https://en.wikipedia.org/wiki/Daraxonrasib

The three Ras genes in humans (HRAS, KRAS, and NRAS) are the most common oncogenes in human cancer; mutations that permanently activate Ras are found in 20–25% of all human tumors and up to 90% in certain types of cancer (e.g., pancreatic cancer).

The first two Ras genes, HRAS and KRAS, were identified from studies of two cancer-causing viruses of the Gammaretrovirus genus, the Harvey sarcoma virus and Kirsten sarcoma virus, by Edward Scolnick and colleagues at the National Institutes of Health (NIH). These viruses were discovered originally in rats during the 1960s by Jennifer Harvey and Werner H. Kirsten, respectively, hence the name Rat sarcoma.

In 1982, activated and transforming human ras genes were discovered in human cancer cells by Geoffrey M. Cooper at Harvard, Mariano Barbacid and Stuart A. Aaronson at the NIH, Robert Weinberg at MIT, and Michael Wigler at Cold Spring Harbor Laboratory. A third ras gene was subsequently discovered by researchers in the group of Robin Weiss at the Institute of Cancer Research, and Michael Wigler at Cold Spring Harbor Laboratory, named NRAS, for its initial identification in human neuroblastoma cells.

The three human ras genes encode extremely similar proteins made up of chains of 188 to 189 amino acids.

The two switch motifs, G2 (SW1) and G3 (SW2), are the main parts of the protein that move when GTP is hydrolyzed into GDP. This conformational change by the two switch motifs is what mediates the basic functionality as a molecular switch protein. This GTP-bound state of Ras is the “on” state, and the GDP-bound state is the “off” state.

Ras is a guanosine-nucleotide-binding protein. Specifically, it is a single-subunit small GTPase, which is related in structure to the Gα subunit of heterotrimeric G proteins (large GTPases). G proteins function as binary signaling switches with “on” and “off” states. In the “off” state it is bound to the nucleotide guanosine diphosphate (GDP), while in the “on” state, Ras is bound to guanosine triphosphate (GTP), which has an extra phosphate group as compared to GDP. This extra phosphate holds the two switch regions in a “loaded-spring” configuration (specifically the Thr-35 and Gly-60). When released, the switch regions relax which causes a conformational change into the inactive state. Hence, activation and deactivation of Ras and other small G proteins are controlled by cycling between the active GTP-bound and inactive GDP-bound forms.

Ras is attached to the cell membrane owing to its prenylation and palmitoylation (HRAS and NRAS) or the combination of prenylation and a polybasic sequence adjacent to the prenylation site (KRAS).

Mutations in the Ras family of proto-oncogenes (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20–30% of all human tumors. It is reasonable to speculate that a pharmacological approach that curtails Ras activity may represent a possible method to inhibit certain cancer types. Ras point mutations are the single most common abnormality of human proto-oncogenes. Ras inhibitor trans-farnesylthiosalicylic acid (FTS, Salirasib) exhibits profound anti-oncogenic effects in many cancer cell lines.

Ras-targeted cancer treatments

Reovirus was noted to be a potential cancer therapeutic when studies suggested it reproduces well in certain cancer cell lines. It replicates specifically in cells that have an activated Ras pathway (a cellular signaling pathway that is involved in cell growth and differentiation). Reovirus replicates in and eventually kills Ras-activated tumour cells and as cell death occurs, progeny virus particles are free to infect surrounding cancer cells. This cycle of infection, replication and cell death is believed to be repeated until all tumour cells carrying an activated Ras pathway are destroyed.

Another tumor-lysing virus that specifically targets tumor cells with an activated Ras pathway is a type II herpes simplex virus (HSV-2) based agent, designated FusOn-H2. Activating mutations of the Ras protein and upstream elements of the Ras protein may play a role in more than two-thirds of all human cancers, including most metastatic disease. Reolysin, a formulation of reovirus, and FusOn-H2 are currently in clinical trials or under development for the treatment of various cancers. In addition, a treatment based on siRNA anti-mutated K-RAS (G12D) called siG12D LODER is currently in clinical trials for the treatment of locally advanced pancreatic cancer (NCT01188785, NCT01676259).

https://en.wikipedia.org/wiki/Ras_GTPase

NOTE: Biochemistry is pretty much beyond my skill level.

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