Jadomycins: A potential chemotherapy for multi-drug resistant metastatic breast cancer.

Esther P Bonitto, Brendan T McKeown, Kerry B Goralski

Pharmacology research & perspectives 2021 Dec

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Breast cancer causes the most cancer fatalities in women worldwide. Approximately one-third of breast cancers metastasize, or spread from primary tumors to other tissues, and have a 70% 5-year mortality rate. Current breast cancer treatments like doxorubicin and paclitaxel become ineffective when breast cancer cells develop multi-drug resistance and overexpress ATP-binding cassette transporters, as the transporters cause a substantial efflux of the chemotherapies. Jadomycins, a group of molecules isolated from Streptomyces venezuelae ISP5230, are shown to be cytotoxic against a variety of cancers, especially breast cancer. Furthermore, jadomycins retain their cytotoxic properties in multi-drug resistant breast cancer cells, as they are not expelled through ATP-binding cassette transporters. Here, we describe the research that supports the potential use of jadomycins as a novel chemotherapy in the treatment of multi-drug resistant, metastatic breast cancer. We present the supportive findings, as well as the mechanisms of action investigated thus far. These include copper-mediated reactive oxygen species generation, aurora B kinase inhibition, and topoisomerase IIα and IIβ inhibition. We also suggest future directions of jadomycin research, which will help to determine if jadomycins can be used as a breast cancer chemotherapy in clinical practice. © 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.

Citation

Esther P Bonitto, Brendan T McKeown, Kerry B Goralski. Jadomycins: A potential chemotherapy for multi-drug resistant metastatic breast cancer. Pharmacology research & perspectives. 2021 Dec;9(6):e00886