Abstract
Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, in the treatment of platinum-resistant ovarian cancer.
Highlights
Ovarian cancer is the fifth deadliest malignancy in US women
EC8042 displayed significant anti-tumor activity against ovarian cancer cell lines with significantly lower toxicity to fibroblasts and peripheral blood cells compared to mithramycin; while strongly inhibiting Specificity protein 1 (Sp1) transcription and reduction in several genes implicated in tumorigenesis including VEGF, BRCA2, cMyc, and src [38,70]
There is ample evidence to suggest that mithramycin is a potent Sp-1 inhibitor and has demonstrated anticancer effects across a wide range of malignancies, including ovarian, in pre-clinical models
Summary
Ovarian cancer is the fifth deadliest malignancy in US women. In 2020, an estimated. In the setting of platinum-resistant disease, single-agent chemotherapy response rates are
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