Revolution Medicines and Daraxonrasib
Some pretty incredible cancer drug news came out last week. Revolution Medicines announced the results of their Phase 3 RASolute 302 clinical trial and their drug, daraxonrasib, demonstrated a median overall survival of 13.2 months versus 6.7 months for chemotherapy for their stage 4 pancreatic cancer patients.
If you’ve not seen it, I urge you to listen to this fantastic NY Times podcast episode between Ross Douthat and Ben Sasse. Sasse, recently diagnosed with Stage 4 pancreatic cancer, saw his tumors shrink 75% due to the drug.
“In mid-December I got a three- to four-month life expectancy, and I’m at Day 99 or something since then, and I’m doing a heck of a lot better than I was doing at Christmas.” – Ben Sasse
RAS-addicted cancers#
Revolution Medicines explains on their website that they develop targeted therapies for patients with “RAS-addicted cancers.” What is a RAS-addicted cancer?
RAS addicted cancers depend on RAS proteins for their survival and growth. RAS stands for rat sarcoma, which is an oncogene. This specific oncogene, when mutated, is responsible for millions of cancer cases across the world each year. “RAS mutations are most commonly found in lung, pancreatic, and colorectal cancer. They are present in about one in four lung cancer cases, more than half of colorectal cancer cases, and nine out of ten pancreatic cancer cases.” 1
When a cancer is RAS-addicted, the tumor relies so heavily on the RAS protein being turned “on”, that any kill switch to that mechanism means the tumor is doomed to shrink. And this sounds so very simple. Turn this thing the cancer so desperately needs off, and that’s it. But for many decades, this protein has been deemed “undruggable”, which means untouchable. Apparently, the surface of RAS proteins is very smooth and that’s why it’s difficult for therapies to bind directly to the cells.
Daraxonrasib#
So, how does RevMed’s daraxonrasib drug work? Instead of binding directly to RAS proteins, the ones with the undruggable smooth surface, daraxonrasib binds to a nice little chaperone protein: Cyclophilin A.
Cyclophilin A’s surface is complementary to parts of a RAS protein surface. So there you have it. The drug attaches to the chaperone, and the chaperone more easily attaches to the target and then, daraxonrasib turns the RAS protein OFF.
Why is it called daraxonrasib? Drug naming is interesting. Names must encode what the drug is and of course, they must be unique so they’re not mixed up in clinical settings.
rasib: RAS inhibitoron: targets the RAS protein in its ON statedarax: I’m not sure, but maybe added to make it more pronouncable and unique
Let’s keep funding science, please#
The Trump administration cut ~$2.7B of NIH funding in the beginning of 2025. This cut included a 31% decrease in cancer research funding compared to the same period the previous year. And the proposed budget for 2026 includes a 37% reduction in funding. While RevMed did not receiving NIH funding for the R&D on daraxonrasib, much of the underlying foundational scientific knowledge around this treatment mechanism was in fact funded via the NIH:
- how RAS mutations cause cancer
- AlphaFold protein structure
- understanding of cyclophilin A
And without this knowledge, daraxonrasib could never be developed. This is why it’s important to fund science.
A little disclosure#
No, I am not a biomedical engineer, oncologist, clinical study coordinator, or anything of the sort. I’m just a nerd who was very recently a caregiver to my husband with Hodgkin’s Lymphoma.