FDA-Approved Breast Cancer Drug Shows Promise for Treating Rare Appendix Cancer

Researchers at the University of California San Diego School of Medicine have uncovered a promising new use for a well-known breast cancer drug: treating a rare form of appendix cancer. This discovery could open up new treatment options for patients facing limited choices.

In a clinical trial published on October 16, 2024, in the Journal of Clinical Oncology, the drug palbociclib, an FDA-approved oral medication for breast cancer, showed its ability to stabilize tumor growth and reduce blood tumor markers in patients with peritoneal mucinous carcinomatosis (PMC)—a rare and aggressive form of cancer originating in the appendix. PMC is often resistant to traditional chemotherapy, making this breakthrough especially significant.

Appendix Cancer: A Rare and Aggressive Disease

Appendix cancer is incredibly uncommon, representing less than 1% of all gastrointestinal cancers. According to the American Cancer Society, fewer than 2,000 cases are diagnosed each year in the U.S. This cancer often goes unnoticed until it has spread to other areas of the body, making treatment especially challenging. One type of appendix cancer, peritoneal mucinous carcinomatosis (PMC), is known for its resistance to chemotherapy, which leaves patients with very limited treatment options.

This is why the discovery that palbociclib, a drug already widely used in treating breast cancer, is effective in managing this rare cancer is so exciting. "Finding that a breast cancer drug is successful in treating a subset of appendix cancer—where treatment options are currently limited—marks a significant advancement in our fight against this disease," said Dr. Andrew Lowy, co-senior author of the study and professor in the Department of Surgery at UC San Diego School of Medicine.

The Promise of Palbociclib for Appendix Cancer

The study involved 16 patients diagnosed with PMC, most of whom had not responded to previous treatments. Researchers analyzed the genetic mutations in these cancers and discovered that those with mutations in the GNAS gene responded well to palbociclib. Remarkably, blood markers associated with cancer activity dropped in more than 80% of these patients.

Palbociclib works by inhibiting cancer cell multiplication, and the study found that it could slow or stop tumor growth in patients with PMC. Even better, the drug is generally well-tolerated compared to traditional chemotherapy, which is known to cause severe side effects.

"This medication can be implemented immediately without the need to wait for a new drug to be developed or for FDA approval," noted Dr. Shumei Kato, co-senior author of the study and associate professor of medicine at UC San Diego School of Medicine. This is a crucial benefit for patients who are in urgent need of new treatment options.

A Step Forward in Targeted Cancer Therapies

This discovery highlights how reusing existing drugs for new purposes can fast-track the development of treatments for rare diseases. Appendix cancer, particularly PMC, has had few targeted treatment options until now. The success of palbociclib in this trial suggests that it could become the first targeted therapy specifically for this cancer. "The findings signal a promising new era for the treatment of appendix cancer and potentially other rare cancers with similar genetic mutations," Kato added.

Looking to the Future

While the results of this trial are promising, further research is needed. The next steps for researchers will involve exploring whether combining palbociclib with traditional chemotherapy or other newer targeted therapies could enhance its effectiveness even further. This could lead to more comprehensive treatment plans for appendix cancer and other cancers with similar genetic profiles.

As Dr. Diane Simeone, director of Moores Cancer Center at UC San Diego Health, put it, "This groundbreaking study validates our unique position as the only National Cancer Institute (NCI)-designated Comprehensive Cancer Center in the region. Our clinical researchers are leading trials that are identifying promising new treatments and providing hope for patients who previously had few options."

Conclusion

This exciting new study is a testament to the power of repurposing existing drugs to combat rare and challenging diseases like appendix cancer. The discovery that a breast cancer drug can effectively treat a rare form of cancer opens up new possibilities for patients and sets the stage for further advancements in cancer research.

Appendix Cancer Pathophysiology:

• Appendix cancer, especially PMC, is typically resistant to chemotherapy.
• It often spreads within the peritoneal cavity, leading to a buildup of mucinous material, which causes significant complications.
• Genetic mutations, particularly in the GNAS gene, play a key role in the progression of certain appendix cancers, as highlighted by the study.

Next Steps: Researchers plan to further investigate combining palbociclib with other treatments to see if its effectiveness can be enhanced. This combination therapy could become a cornerstone in managing appendix cancer and potentially other rare cancers with similar genetic profiles.

Funding and Acknowledgments: The study received funding from several organizations, including the Levine Family Chancellor’s Endowed Chair in Surgical Oncology and the National Organization for Rare Disorders. Contributions from donors like the Euske Family Foundation and the Gastrointestinal Cancer Research Fund also supported this breakthrough research.

This groundbreaking work offers a beacon of hope for patients with appendix cancer, who until now had limited treatment options. As research continues, patients and their families can look forward to more effective and personalized care strategies.

For more information, visit the University of California - San Diego website or check out the full study in the Journal of Clinical Oncology.