A new study on KRAS inhibition in appendiceal cancer is now published in the Journal of Hematology & Oncology, one of the top journals in cancer medicine. The work comes from Dr. JP Shen’s lab at MD Anderson. Dr. Shen serves on Appendicure’s board, and he shared the news with me directly. The results are promising. They also have real limits.
Why KRAS inhibition in appendiceal cancer matters
KRAS is a gene. When it mutates, it can tell cancer cells to keep growing. It shows up a lot in appendix cancer. In mucinous appendiceal tumors, roughly 80 percent carry a KRAS mutation. The most common version is called G12D. For a long time, KRAS was seen as impossible to drug. That has started to change. New medicines can now block certain KRAS mutations. This study set out to test whether those medicines work against appendix cancer.
What the study found in the lab
Most of the work happened in the lab. The team grew appendix tumors two ways. They used organoids, which are tiny tumor models grown from patient tissue. They also used mice carrying human tumors. Then they tested two KRAS drugs. One is MRTX1133, which targets the G12D mutation. The other is daraxonrasib (RMC-6236), a broader inhibitor that blocks several forms of RAS, not just one mutation. Both drugs strongly suppressed the tumors. The team could see the drugs hit their target and shut down the growth signal. The treated tumors had fewer dividing cells and more cancer cell death.
What the study found in people
The paper also reports early results from a group of 15 patients treated with KRAS inhibitors. The patients were a mix, some had prior treatment and some had not. Among those who could be measured, every one showed a benefit. Tumor markers in the blood came down fast, by an average of more than 80 percent within the first 12 weeks. On imaging, one patient had a complete response, one had a partial response, and the rest had stable disease. For a cancer with so few options, that is a real signal.
“Appendiceal cancer has long lacked effective systemic treatment options, and patients urgently need new approaches. I am very excited about the future prospects of KRAS inhibition. This study is just the first step.” — John Paul Shen, M.D., MD Anderson Cancer Center
The honest part
I don’t want anyone to read more into this than what’s there. Most of the strong results are preclinical. That means they happened in organoids and mice, not in people. Lab results don’t always hold up once a drug reaches patients. The patient group here was small and early. There’s no FDA approval for these drugs in appendix cancer. There’s no appendix-specific trial for these drugs open yet either. These tumors can also adapt and resist the drugs over time. The paper points to a pathway called EMT as one way that resistance takes hold. So the picture is promising, but it isn’t simple.
Why this still matters
Appendix cancer has few proven treatment options. Most standards were borrowed from colon cancer. The 2025 Godfrey consensus guidelines are the closest thing the field has to a standard of care built for appendix cancer, and even those leave big gaps. Research aimed straight at appendix cancer is rare. This study is aimed straight at it. It gives doctors a real target to build on. It also gives this community a reason to push for a trial. This work was peer reviewed, which means independent experts checked it and found it sound. That’s a real step forward.
What happens next
If you or a loved one has a KRAS mutation, this is worth saving to talk through with your oncologist. It’s not a treatment recommendation. It’s a signpost for where the science is heading. KRAS inhibition in appendiceal cancer is still early, but for the first time it is aimed straight at us.
Read more
- KRAS G12D and Appendix Cancer – New Developments
- Appendix Cancer AI: How KRAS Drug Discovery Could Change Treatment
Help move this research forward
One of the best ways to speed up research is data. The Patient-Led Global Appendix Cancer Registry is now IRB-reviewed and collecting information from patients around the world. Your data helps researchers like Dr. Shen ask better questions. Join the registry here:
Join the registry — United States Join the registry — International
Study: Chowdhury S, Ito I, Pattalachinti VK, Yousef AMG, Yousef MMG, El Khoury S, Hornstein N, Seldomridge AN, Hong D, Overman MJ, Taggart MW, Foo WC, Helmink B, Fournier KF, Shen JP. “KRAS inhibition is an effective therapy for appendiceal adenocarcinoma.” Journal of Hematology & Oncology, published July 2, 2026. DOI: 10.1186/s13045-026-01817-3. Read the paper.
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