Unlocking the therapeutic potential of rigosertib as a selective therapy for ovarian cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Precision oncology traditionally targets recurrent mutations, but ovarian cancer's diverse alterations require new strategies.
• Identifying tumor-specific vulnerabilities is crucial for effective ovarian cancer treatment.

Purpose of the Study:

• To develop a functional modeling approach for identifying therapeutic vulnerabilities in ovarian cancer.
• To nominate a novel therapeutic regimen for ovarian tumors by integrating drug screening and signaling pathway analysis.

Main Methods:

• Utilized a functional modeling approach combining drug screening with Kinome Atlas-based signaling assessment.
• Evaluated the efficacy of rigosertib, a small-molecule RAS mimetic, and its combinations in ovarian cancer models.

Main Results:

• Rigosertib demonstrated tumor-selective activity in ovarian cancer.
• Combination therapy of rigosertib with phosphoinositide 3-kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitors prevented survival signaling and induced tumor regressions in xenografts.

Conclusions:

• The combination of rigosertib with PI3K or mTOR inhibitors represents a promising therapeutic strategy for ovarian cancer.
• Further clinical investigation of these combinations is warranted for ovarian cancer treatment.