The Potential of Existing Drugs in Treating Oral and Esophageal Cancers

In a groundbreaking study published in Molecular Cancer Research, a team of researchers from the Tokyo Medical and Dental University (TMDU) has uncovered novel therapeutic strategies using existing drugs for treating oral and esophageal carcinomas. This discovery holds significant promise for improving the survival rates and outcomes for patients suffering from these forms of cancer.

The Scope of Oral and Esophageal Cancers

According to the Oral Cancer Foundation, over 53,000 Americans will be diagnosed with oral or oropharyngeal cancer in 2023. Unfortunately, the five-year survival rate for these cancers is only around 57%. Oral cancer typically manifests as a growth in the mouth, including the gums, lips, and the posterior portions of the mouth and throat.

The American Cancer Society estimates that there are about 18,440 new cases of esophageal cancer in the United States each year, with approximately 16,170 deaths. Notably, while your dental professional can check for oral cancer during dental checkups, esophageal cancer currently lacks a screening tool. This type of cancer occurs in the esophagus, a tube-like organ that connects your throat to your stomach and plays a vital role in transporting food and liquids through your body.

New Therapeutic Strategies Using Existing Drugs

In the latest study, researchers combined two existing drugs—pitavastatin and capmatinib—to effectively inhibit the growth and viability of oral cancer cells in culture and in a mouse model of esophageal cancer. These drugs were tested on a highly metastatic oral cancer cell line. Overall, pitavastatin proved to be the most effective in reducing tumor growth, with capmatinib playing a supportive role in targeting the MET signaling pathway.

Pitavastatin: A Cholesterol-Lowering Agent

Pitavastatin is a dihydroxy monocarboxylic acid with the chemical structure 6E-7-[2-cyclopropyl-4-fluorophenylquinolin-3-yl]hept-6-enoic acid, and it is the 3R5S-stereoisomer. This medication is a relatively recently developed cholesterol-lowering agent. It works by inhibiting the enzyme HMG-CoA reductase, which is involved in cholesterol biosynthesis. By inhibiting this enzyme, pitavastatin reduces the production of cholesterol and helps control high blood cholesterol levels.

Capmatinib: An Effective MET Inhibitor

Capmatinib is a small molecule kinase inhibitor that targets c-Met, also known as the hepatocyte growth factor receptor (HGFR). c-Met is a receptor tyrosine kinase involved in signaling cascades critical for organ regeneration and tissue repair. In healthy individuals, this receptor activates these cascades, but in many cancers, including some cases of esophageal and lung cancer, c-Met becomes overactive, contributing to tumor progression and metastasis. Capmatinib is currently used to treat non-small cell lung cancer (NSCLC) in patients whose tumors have a specific MET exon 14 skipping mutation.

The Research Findings

The researchers conducted a comprehensive drug screening on the highly metastatic oral cancer cell line. Their results showed that the combination of pitavastatin and capmatinib significantly inhibited the viability and growth of these cells, both in culture and in the mouse model. Molecular analysis revealed that pitavastatin primarily inhibited the MET signaling pathway, with capmatinib serving to enhance the effectiveness of this inhibition.

These findings suggest that existing drugs, when used in combination, can be repurposed as effective treatments for oral and esophageal cancers. The combination of pitavastatin and capmatinib potentially offers a novel therapeutic strategy that could improve patient outcomes and survival rates.

Conclusion

The ongoing research in repurposing existing drugs to treat cancers is showing promising results. The combination of pitavastatin and capmatinib, as demonstrated in the TMDU study, represents a significant advance in the treatment of oral and esophageal carcinomas. Further clinical trials are needed to confirm these findings and explore the full potential of these drugs in oncology.