Normalizing the Tumor Microenvironment: A New Frontier in Ovarian Cancer Therapy

TL;DR

This review explores how normalizing the tumor environment in ovarian cancer could improve treatment outcomes by enhancing chemotherapy and immunotherapy.

Contribution

The paper highlights the novel use of extracellular matrix normalization to synergize with existing therapies in advanced ovarian cancer.

Findings

Abnormal tumor microenvironment hinders effective ovarian cancer treatment.

Extracellular matrix normalization shows synergistic benefits with chemotherapy and immunotherapy in preclinical models.

TME normalization is a promising strategy to overcome chemoresistance and immunosuppression.

Abstract

Ovarian cancer is one of the deadliest gynecological malignancies, where most patients become clinically symptomatic at advanced stages of disease due to the lack of effective diagnostic screening. Despite recent advances in surgical resection and chemotherapy, recurrent ovarian cancer remains largely refractory to treatment, resulting in poor prognosis. The ovarian cancer tumor microenvironment (TME) is highly abnormal and presents a significant barrier to successful therapy. A combination of abnormal vasculature, desmoplastic extracellular matrix, and aberrantly activated hypoxic and immune-suppressive pathways culminates in promoting tumor growth, dissemination, chemoresistance, and immunosuppression. Whilst immune checkpoint inhibitors have shown success in other cancers, their application in ovarian cancer, particularly at advanced stages, remains limited. In this review, we discussed the application of tumor extracellular matrix normalizing therapies in preclinical models of advanced ovarian cancer, and their synergistic benefit to chemotherapy and immunotherapy. Collectively, these insights underscore TME normalization as a promising therapeutic strategy with the potential to improve ovarian cancer management.

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