Novel Systems Biology Approach to Decoding Actionable Targets to Overcome Resistance in GI Cancer Monotherapies
Abstract
Gastrointestinal (GI) cancer patient responses to treatment are extremely heterogeneous across patient populations, and resistance to current drug therapies often occurs after a short period. Thus, it is urgent to identify new drug combination targets for improving prognosis in a large number of GI cancer patients. GI cancer is more common in military members due to exposure to carcinogens in the field including certain chemicals and ionizing radiation. This type of exposure causes mutations in DNA which increases the rate of cancer development. We have previously shown that heterogeneous cancer mutations potentiate tumor-specific responses through distinct mechanisms and interactome network perturbations. While most of the current methodologies focus on predicting single targets to fight against tumors, few have therapeutic value in designing combination targets. During this reporting period, wehave developed a network-based approach integrating functional variomics and synthetic lethality, and identified novel candidate actionable drug combinations for GI cancer. We hypothesize that combination modulation of GI tumors co-treated with MEK and PARP inhibitors will promote reduction of GI tumors compared to single agents alone. The proposed combination therapy, then, islikely to be most effective in military members with GI cancers as their tumors are likely to carry drug-resistant mutations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1152643
Entities
People
- Nidhi Sahni
Organizations
- University of Texas at Austin