HIF-1α Is a Rational Target for Future Ovarian Cancer Therapies

Abstract

Ovarian cancer is the eighth most commonly diagnosed cancer among women worldwide. Even with the development of novel drugs, nearly one-half of the patients with ovarian cancer die within five years of diagnosis. These situations indicate the need for novel therapeutic agents for ovarian cancer. Increasing evidence has shown that hypoxia-inducible factor-1α(HIF-1α) plays an important role in promoting malignant cell chemoresistance, tumour metastasis, angiogenesis, immunosuppression and intercellular interactions. The unique microenvironment, crosstalk and/or interaction between cells and other characteristics of ovarian cancer can influence therapeutic efficiency or promote the disease progression. Inhibition of the expression or activity of HIF-1α can directly or indirectly enhance the therapeutic responsiveness of tumour cells. Therefore, it is reasonable to consider HIF-1α as a potential therapeutic target for ovarian cancer. In this paper, we summarize the latest research on the role of HIF-1α and molecules which can inhibit HIF-1α expression directly or indirectly in ovarian cancer, and drug clinical trials about the HIF-1α inhibitors in ovarian cancer or other solid malignant tumours.

Computed Tomography Imaging-Based Radiogenomics Analysis Reveals Hypoxia Patterns and Immunological Characteristics in Ovarian Cancer

“…Most previous studies focused on single regulators about hypoxia in OC. For example, hypoxia-inducible factor-1α (HIF-1α) has been proven to play an important role in promoting OC chemoresistance, tumor metastasis, and immunosuppression ( 56 ). The high expression of maspin induced by hypoxia might be associated with a poor prognosis of ovarian clear cell carcinoma ( 57 ).…”

Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches

“…In addition to its fundamental role in metabolic reprogramming, HIF-1 is involved in chemoresistance, metastasis, angiogenesis, and immunosuppression in cancer cells; therefore, it is emerging as an important therapeutic target [186]. Some drugs have been developed that can intervene in the action of HIF-1, such as SC-144, a pyrroloquinoxaline derivative with broad-spectrum anticancer activity [187], which can reduce HIF-1α expression and increase levels of hypoxia-inducible antisense factor (HIF-1α-AS) after prolonged exposure, and may explain, at least in part, its antitumor activity [188].…”

Clinical Significance of Tie-2-Expressing Monocytes/Macrophages and Angiopoietins in the Progression of Ovarian Cancer—State-of-the-Art

“…One of its distinctive features is hypoxia. According to literature data, hypoxia is involved in processes such as tumour growth, angiogenesis, resistance to apoptosis, and chemotherapy, as well as metastasis [ 20 ]. The ECM includes chemokines, inflammatory cytokines, integrins, and MMPs.…”