Untapped Therapeutic Targets in the Tumor Microenvironment
Abstract
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 would inhibit tumor progression and/or increase chemotherapeutic efficacy. Using three different approaches to targeting CAFs in an immunocompetent mouse model of ovarian cancer that was developed in our laboratory, we failed to show any significant benefits of targeting CAFs. We realized that we needed to develop a more fibrotic model of ovarian cancer to demonstrate the efficacy of anti-fibrotic agents. During this funding period, we generated two new mouse models, both of which exhibit extensive fibrosis and rapid onset of ovarian carcinomatosis. We are currently testing anti-fibrotic agents in these improved mouse models. We also made significant advances in characterizing the functional properties ofCOL11A1, which we previously identified as a molecular target that distinguishes CAFs from other fibroblasts.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 31, 2018
- Accession Number
- AD1074305
Entities
People
- Sandra Orsulic
Organizations
- Cedars-Sinai Medical Center