APPENDICURE

A new biobank of patient-derived appendix cancer models is the first of its kind. Here is what the research found, and what it does and does not mean for patients right now.

Appendix cancer organoids, grown in the lab from patient tumors, are giving researchers their first real tool for studying this rare disease on its own terms. Appendix cancer has always been hard to study. It is rare, so few labs work on it. The tumors are often packed with mucus and contain relatively few actual cancer cells, which makes them difficult to test and even to sequence accurately. And for years, the drugs given to patients were borrowed almost entirely from colon cancer, on the assumption that what works in the colon should work in the appendix. That assumption has never been well supported by evidence.

A study published in Developmental Cell in June 2026, led by Karuna Ganesh’s lab at Memorial Sloan Kettering Cancer Center, takes a direct run at all three of those problems. The team built the first stable, long-term biobank of appendix cancer organoids grown from patient tumors. Using those models, they found mutations that standard clinical sequencing had missed, and they identified two drugs that worked against the cancer in the lab and in mice where standard chemotherapy did not. The paper is open access, so anyone can read it in full.

The whole point of the study is that appendix cancer is not colon cancer, and treating it as if it were has real costs.

What the appendix cancer organoids actually are

When researchers want to test cancer drugs before trying them in people, they need a living model of the disease. For most common cancers, those models already exist and can be grown indefinitely in the lab. For appendix cancer, they essentially did not. That gap is part of why progress has been slow.

The MSK team collected tumor tissue from 24 patients during surgery and grew it into organoids, which are small three-dimensional clusters of cells that reproduce the structure and behavior of the original tumor. Out of those samples, they established 16 organoid lines that could be frozen, thawed, and regrown over and over. That durability is what makes a biobank useful, because the same model can be shared, repeated, and tested by many groups over time.

Importantly, three of the lines came in matched pairs: one organoid grown from a patient’s primary appendix tumor, and another grown from that same patient’s peritoneal metastasis, the disease that had spread into the abdominal cavity. Comparing the two sides by side, from the same person, is what allowed the researchers to ask what changes when this cancer spreads.

One detail is worth stating plainly, because it shapes how broadly these findings apply. The appendix cancer organoids grew most successfully from poorly differentiated, higher-grade tumors. Well-differentiated and moderately differentiated tumors mostly failed to form stable models. So the biobank leans toward the more aggressive end of the disease, and the drug findings below are most relevant there. This is not a study about low-grade appendix cancer or classic pseudomyxoma peritonei, and it should not be read as one.

Finding one: appendix cancer organoids surface mutations the standard test misses

This is the finding with the most immediate relevance to patients, and it is worth understanding carefully.

When a tumor is sent for genomic testing, the lab looks for mutations that might guide treatment. But those tests have a detection floor. The clinical sequencing platform used here, MSK-IMPACT, generally needs a mutation to show up in at least about 5 percent of the genetic material in the sample before it gets called. In most cancers that is fine. In appendix cancer it is a real problem, because so much of the sample is mucus and normal tissue rather than cancer cells. When the cancer cells are diluted, a genuine mutation can sit below that floor and never get reported.

Growing the tumor as an organoid concentrates the cancer cells, which raises the proportion of cancer DNA in the sample. When the researchers sequenced the appendix cancer organoids, they found mutations, including KRAS mutations linked to worse outcomes, that the standard clinical test had not called from the original tissue. Going back and manually re-examining the original sequencing data confirmed those mutations had been there all along, just below the reporting threshold.

The practical takeaway is not that current testing is useless. It is that a negative result in a mucinous, low-cellularity appendix tumor may not be the final word, and that there are emerging ways to get a cleaner read. This is a reasonable thing for patients to discuss with their oncologist, especially when a targeted-therapy decision hinges on whether a mutation is present.

A negative genomic result in a mucus-heavy appendix tumor may reflect the limits of the test, not the absence of a mutation.

Finding two: targeted drugs outperformed the borrowed colon-cancer chemo

Tested against the appendix cancer organoids, the standard chemotherapy regimens patients have long received, which were originally developed for colon cancer, were largely ineffective, and the metastatic organoids were especially resistant. That result lines up with what many patients and clinicians have observed, and it strengthens the case that appendix cancer needs its own treatment strategies rather than colon cancer’s hand-me-downs.

The researchers then tested drugs aimed at the specific signaling pathways that these tumors appear to depend on. Two stood out. The first, RMC-7977, blocks RAS, a signaling protein driven by the KRAS mutations that are common in appendix cancer. The second, WNTinib, targets the Wnt pathway, another growth signal the tumors rely on. Both reduced tumor growth in the lab, and both reduced disease in mice. They worked best in the adjuvant setting, meaning as a short course aimed at wiping out residual cancer cells after cytoreductive surgery, which is exactly the moment when recurrence tends to take hold.

There is a real translational thread here, and it is worth being precise about it. RMC-7977 is a close analog of a drug called daraxonrasib (RMC-6236), which is already being tested in humans and has received FDA breakthrough therapy designation in pancreatic cancer. So the underlying approach is not science fiction. But, and this matters, those human trials are in pancreatic and lung cancer, not appendix cancer. RMC-7977 itself, the exact compound used in this study, remains a preclinical research tool.

What this means, and what it does not

It is easy to read a study like this and hear “new treatment.” That is not what this is, and being honest about the gap is the most useful thing this post can do.

Everything in the drug portion of this work happened in organoids and in mice. No appendix cancer patient was treated with these drugs in this study. Lab and animal results frequently look more promising than what later plays out in people, which is the entire reason clinical trials exist. The path from a mouse result to an approved therapy is long, and most candidates do not complete it.

What the study genuinely provides is a foundation. It gives researchers, for the first time, a stable and shareable set of appendix cancer organoids that behave like the real disease. It offers a credible rationale for designing appendix-specific trials, particularly trials testing RAS-directed drugs after surgery in patients whose tumors carry the relevant mutations. And it delivers a concrete, present-day point for patients: in mucinous appendix tumors, standard genomic testing can undercall mutations, and that is worth a conversation with your care team.

For a rare cancer that has spent decades borrowing from its more common neighbor, having models that finally let researchers study the disease on its own terms is meaningful progress. The drugs may or may not pan out. The tools to find out now exist, and that is the part that lasts.

The Study

Mahmoud A, Sukhwa C, Giarrizzo M, et al. “An appendiceal cancer organoid biobank identifies phenotypic evolution and druggable dependencies of peritoneal carcinomatosis.” Developmental Cell, June 10, 2026. Open access.

Read the full study at Developmental Cell →

If you or a loved one is living with appendix cancer, your experience can help shape research like this. Consider adding your information to the Appendicure patient data registry.

Appendicure provides patient education and does not offer medical advice. Talk with your own care team about decisions related to testing and treatment.