Untapped Therapeutic Targets in the Tumor Microenvironment
Technical Report,01 Aug 2016,31 Jul 2017
Cedars-Sinai Medical Center Los Angeles United States
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Most therapeutic approaches have focused on the tumor cell and its genetic alterations. However, it is becoming clear that the microenvironment plays an important role in tumor evolution. We hypothesized that conventional chemotherapy for ovarian cancer will be more effective if the microenvironment that harbors the resistant cancer cells is simultaneously targeted. Since activated carcinoma-associated fibroblasts CAFs have a prominent role in most aspects of tumor progression, including responses to anticancer agents by forming a physical barrier that prevents chemotherapy access and promotes resistance, we predicted that targeting CAFs will inhibit tumor progression andor increase chemotherapeutic efficacy. We used three different approaches to target CAFs in an immunocompetent mouse model of ovarian cancer that was developed in our laboratory. In this first funding period, we have optimized the preclinical trial design and developed an efficient pipeline for the collection of tissues from tumors and major organs that may be affected by CAF-targeted therapies. We have tested three drugs that target different molecular aspects of CAF activation. Although the tested drugs did not have significant effects on disease onset or survival in mice, the pending analyses of the collected tissues will provide key information about the possible cellular and molecular effects of these drugs on the tumor microenvironment.
- Medicine and Medical Research
- Anatomy and Physiology