Rational Development of Immune Therapy for Low-Grade Ovarian Serous Carcinoma to Overcome MEK Inhibitor Resistance
Abstract
Low-grade serous ovarian cancer accounts for a relatively large percentage of epithelial ovarian cancers in young women. The exact biological pathways that underlie this disease are elusive. Moreover, chemotherapy and hormonal therapy are relatively ineffective and have generally failed to reduce high morbidity and mortality. Because the Ras/Raf/MEK/ERK pathway is frequently activated in LGSC, targeting this pathway has been examined as an avenue for potential treatment. Inthe phase II GOG0239 clinical trial, 52 patients were treated with the MEK inhibitor (MEKi), selumetinib. Of these, one had a complete response, seven had a partial response, and 34 had stable disease. Unfortunately, all the patients with stable disease eventually developed resistance to MEKi and died of the disease. This study is investigating the immune pathway and how the immune pathway responds to MEK inhibitor in low-grade ovarian serous carcinoma (LGSC). The immune profile oflow-grade serous cancer is largely unknown, and how the immune profile will be affected by currently targeted therapy in clinical trial using MEK inhibitors is also unclear. By deciphering how targeted therapy may affect the immune system in LGSC, rational design of clinical trials by combining targeted therapy and immunotherapy will be possible to improve low-grade ovarian serous cancer patient survival.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1110629
Entities
People
- Kwong K. Wong
Organizations
- The University of Texas MD Anderson Cancer Center