Abstract
Despite several advances in the understanding of ovarian cancer pathobiology, in terms of driver genetic alterations in high-grade serous cancer, histologic heterogeneity of epithelial ovarian cancer, cell-of-origin for ovarian cancer, the survival rate from ovarian cancer is disappointingly low when compared to that of breast or prostate cancer. One of the factors contributing to the poor survival rate from ovarian cancer is the development of chemotherapy resistance following several rounds of chemotherapy. Although unicellular drug resistance mechanisms contribute to chemotherapy resistance, tumor microenvironment and the extracellular matrix (ECM), in particular, is emerging as a significant determinant of a tumor’s response to chemotherapy. In this review, we discuss the potential role of the tumor microenvironment in ovarian cancer recurrence and resistance to chemotherapy. Finally, we propose an alternative view of platinum-sensitive recurrence to describe a potential role of the ECM in the process.
Highlights
Despite several advances in the understanding of ovarian cancer pathobiology, in terms of driver genetic alterations in high-grade serous cancer, histologic heterogeneity of epithelial ovarian cancer, cell-of-origin for ovarian cancer, the survival rate from ovarian cancer is disappointingly low when compared to that of breast or prostate cancer
Unicellular drug resistance mechanisms contribute to chemotherapy resistance, tumor microenvironment and the extracellular matrix (ECM), in particular, is emerging as a significant determinant of a tumor’s response to chemotherapy
TUMOR DORMANCY AS A MECHANISM OF PLATINUM-SENSITIVE RECURRENCE In addition to putative cancer stem cells that exist as quiescent, dormant, or intrinsically resistant tumor cells that persist through chemotherapy and repopulate the tumor after chemotherapy, some tumor cells may enter dormancy due to specific tumor microenvironment
Summary
Despite several advances in the understanding of ovarian cancer pathobiology, in terms of driver genetic alterations in high-grade serous cancer, histologic heterogeneity of epithelial ovarian cancer, cell-of-origin for ovarian cancer, the survival rate from ovarian cancer is disappointingly low when compared to that of breast or prostate cancer. We discuss the potential role of the tumor microenvironment in ovarian cancer recurrence and resistance to chemotherapy. It is difficult to apply this simplistic model to platinum-sensitive recurrent disease because not all tumor cells that persist through initial rounds of chemotherapy become resistant to chemotherapy.
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