Mithramycin and Analogs for Overcoming Cisplatin Resistance in Ovarian Cancer
David Schweer,
J. Robert McCorkle,
Jurgen Rohr,
Oleg V. Tsodikov,
Frederick Ueland,
Jill Kolesar
Affiliations
David Schweer
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Lexington, University of Kentucky Markey Cancer Center, Lexington, KY 40536, USA
J. Robert McCorkle
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
Jurgen Rohr
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
Oleg V. Tsodikov
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
Frederick Ueland
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Lexington, University of Kentucky Markey Cancer Center, Lexington, KY 40536, USA
Jill Kolesar
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Lexington, University of Kentucky Markey Cancer Center, Lexington, KY 40536, USA
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.
