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.
Highlights
Ovarian cancer is the eighth most commonly diagnosed cancer among women worldwide [1]
With the uncontrolled growth of tumour cells and abnormalities in tumour microcirculation [9], hypoxia is an obvious feature of the tumour microenvironment (TME), which is positively associated with tumour growth, angiogenesis, resistance to apoptosis and chemotherapy, and tumour metastasis [10]
In the ovarian cancer microenvironment, various factors can regulate the expression of Hypoxia-inducible factors (HIFs)-1a expression in nontumour cells and affect the malignant biological properties of tumour cells
Summary
Ovarian cancer is the eighth most commonly diagnosed cancer among women worldwide [1]. Numerous studies have indicated that the TME plays a vital role in the malignant biological properties of tumours [6, 7], including ovarian cancer [8]. Considering the constitutive expression of the b subunit, targeting HIF-1a may be a novel approach to treat ovarian cancer. Alabiad et al reported a good response to chemotherapy in patients with low HIF-1a expression [33]. Considering the large number of cell experiments proving that HIF-1a contributes to the chemoresistance of ovarian cancer (discussed later) and the small number of samples in the studies mentioned previously, we need to further investigate the relationship between HIF-1a expression and chemotherapy sensitivity (Table 1). As an important tumour suppressor, p53 plays an important role in modulating drug sensitivity [39,40,41].After mimicking hypoxic
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