1. < Pancreatic Cancer

Promising news on targeting KRAS G12D mutations

Posted by markymarkfl @markymarkfl, Mar 14 4:19pm

[Edit: As noted in another thread, the Guardant 360 blood test never identified a KRAS G12D mutation in my sample, but a Tempus tissue test of post-Whipple tissue did. This suggests to me (non-medically trained) the tissue test may be more sensitive, or at least otherwise more likely to detect this solid tumor mutation than a blood test. Could be of possible value in identifying trials & treatments. Consider the PanCan.org "Know Your Tumor" program.]

I spotted this March 5, 2024 article a few days ago:
https://www.genengnews.com/topics/cancer/pancreatic-cancer-drug-candidate-targets-elusive-but-common-k-ras-variant/
which cites this paper
https://www.nature.com/articles/s41589-024-01565-w
which offers a link to download the .pdf file here:
https://www.nature.com/articles/s41589-024-01565-w.pdf
Highlights from the first link:

"K-Ras mutations are extremely common in pancreatic cancer, explaining 90% of cases. Nearly half of all pancreatic cancers are caused by K-Ras-G12D"

So far it's only in test-tube and mouse models, but

"The scientists are now optimizing the molecule to be durable enough to fight cancer in the human body. With the traction gained from this study, Shokat said, new therapies for pancreatic cancer could enter clinical trials in as little as two to three years."

HANG IN THERE, MY FRIENDS!
..
FWIW, a few other interesting links turned up:
https://www.mirati.com/science/programs/kras-inhibitors/kras-g12d-inhibitor/
..
https://www.cancer.gov/news-events/cancer-currents-blog/2023/pancreatic-cancer-kras-g12d-mrtx1133
..
https://www.nature.com/articles/s41417-022-00561-3
..
Mirati was acquired by Bristol Myers Squibb in October 2023.
..
https://www.pharmaceutical-technology.com/data-insights/bristol-myers-squibb-files-patent-for-inhibitors-of-kras-g12d/
..
https://www.bioworld.com/articles/706349-us-researchers-identify-new-gtpase-kras-g12d-mutant-inhibitors?v=preview
(Requires account & login)
..
https://www.msn.com/en-us/health/other/mits-albumin-based-cancer-vaccine-shows-promising-results-in-trials/ar-BB1irdlu
..
https://clinicaltrials.gov/study/NCT04853017
https://finance.yahoo.com/news/lilly-announces-details-presentations-2024-220000702.html
"Eli Lilly and Company (NYSE: LLY) today announced that preclinical data for agents targeting Nectin-4, KRAS G12D ... will be presented ... [including] new preclinical data for a fully human monoclonal anti-Nectin-4 antibody conjugated to a novel topoisomerase I inhibitor and a highly potent and orally administered inhibitor of KRAS G12D that is selective against wild-type KRAS."

Recent overview of targeting KRAS in PC:
https://www.researchgate.net/publication/378733526_Targeting_KRAS_in_pancreatic_cancer

Interested in more discussions like this? Go to the Pancreatic Cancer Support Group.

sdd3460 | @sdd3460 | Mar 14 7:09pm

You provide such a wealth of information and positive encouragement. Thank you!

I have recently learned that KRAS p.Q61H mutation is what my family is dealing with. From what I can tell it is a relatively rare one.

Anyone have any experience or insight they’d like to share?

REPLY
1 reply
gamaryanne | @gamaryanne | Mar 20 8:35am

KRAS G12D TRIAL RECRUITING in 6 locations. This is not immunotherapy trial at John’s Hopkins and other places.

Check out Revolution Medicine in San Diego. Trial 9805.
It is in phase 1b and will recruiting for about 6 more weeks. It is close to Phase 2.

Doctor I consulted with said it is looking very good and has the ability to “turn off” this mutation (sorry-I am far from a medical expert so layman’s terms!).

REPLY
1 reply
sdd3460 | @sdd3460 | Mar 22 8:49am
In reply to @gamaryanne "KRAS G12D TRIAL RECRUITING in 6 locations. This is not immunotherapy trial at John’s Hopkins and..." + (show)
@gamaryanne

KRAS G12D TRIAL RECRUITING in 6 locations. This is not immunotherapy trial at John’s Hopkins and other places.

Check out Revolution Medicine in San Diego. Trial 9805.
It is in phase 1b and will recruiting for about 6 more weeks. It is close to Phase 2.

Doctor I consulted with said it is looking very good and has the ability to “turn off” this mutation (sorry-I am far from a medical expert so layman’s terms!).

Jump to this post

Thank you, that is encouraging!

REPLY
stageivsurvivor | @stageivsurvivor | Mar 23 11:08pm
In reply to @sdd3460 "You provide such a wealth of information and positive encouragement. Thank you! I have recently learned..." + (show)
@sdd3460

You provide such a wealth of information and positive encouragement. Thank you!

I have recently learned that KRAS p.Q61H mutation is what my family is dealing with. From what I can tell it is a relatively rare one.

Anyone have any experience or insight they’d like to share?

Jump to this post

For the KRAS Q61 mutation, there is a “pan” KRAS trial using the drug compound RMC-6236 that interrupts the cell signaling pathway upstream from where the KRAS variants occur.

RMC-6236 binds to the RAS molecule which serves as an “off switch” to stop cell growth and proliferation. By having the RNC-6236 bind to RAS, the “switch is turned from ON (unchecked growth and proliferation) to OFF. Occurring upstream of the KRAS Q61 location, the cell signaling pathway is interrupted initiating apoptosis (programmed cell death).

This trial is recruiting at multiple locations in the US and can be found on clinical trials.gov or calling the Pancreatic Cancer Action Network at 877.272.6226, M-F, 7:00am-5:00pm PT.

REPLY
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