Innovative Precision Medicine Strategy Shows Promise for Ovarian Cancer Treatment

Recent research conducted by investigators at Weill Cornell Medicine has uncovered a promising new approach to treating ovarian cancer, a notoriously difficult-to-treat malignancy. The study demonstrates that pairing two experimental drugs can effectively inhibit tumor growth and combat resistance mechanisms that often hinder treatment success.

Ovarian cancer is markedly heterogeneous, driven by diverse genetic mutations that complicate targeted therapy development. Instead of focusing on common mutations, the researchers adopted a novel precision medicine approach that analyzed activation patterns of critical growth signaling pathways within tumor cells.

By examining pathway-level data, the team identified a strategic combination therapy involving an experimental drug called rigosertib, which inhibits the MAPK pathway. This pathway is frequently hyperactive in ovarian tumors, promoting uncontrolled cell growth. Interestingly, inhibiting the MAPK pathway with rigosertib in ovarian cancer cells partially de-repressed the PI3K/mTOR pathway—another route tumors exploit for survival, leading to drug resistance.

To overcome this, the team screened various PI3K/mTOR inhibitors alongside rigosertib. Their findings revealed that combined treatment not only suppresses tumor growth more effectively than either drug alone but also reduces the likelihood of resistance. These encouraging results, obtained from preclinical models, suggest that targeting multiple pathways simultaneously could be a potent strategy against ovarian cancer.

Dr. Benjamin Hopkins, senior author of the study, emphasized the potential impact of this approach, noting that it could be adapted to other cancers that lack highly recurrent targetable mutations. The study’s first author, Dr. Shalini Nath, contributed significant insights into the tumor-specific vulnerabilities that this combination exploits.

Ovarian cancer remains a major health challenge, with nearly 250,000 women living with the disease in the U.S. and about 20,000 new cases annually. The conventional treatment involves surgery followed by chemotherapy, but recurrence is common and survival rates remain modest. Therefore, novel therapeutic strategies are critically needed.

The research team also analyzed existing ovarian tumor datasets and found that many tumors exhibit hyperactivity in the MAPK pathway, making it a promising target. Their screening of drug compounds identified rigosertib as particularly effective, especially when used in combination with PI3K/mTOR inhibitors.

Looking ahead, Dr. Hopkins and colleagues aim to develop more potent drugs targeting these pathways, and to further explore tumor dependencies that could provide additional treatment options, particularly for second-line therapy, as current options are limited.

This innovative research underscores the potential of pathway-focused precision medicine in developing effective, personalized treatments for ovarian cancer and possibly other genetically diverse cancers.