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Mithramycin suppresses DNA damage repair via targeting androgen receptor in prostate cancer

Cancer Lett. 2020-05-01; 
Shan Wang, Collin Gilbreath, Rahul K Kollipara, Rajni Sonavane, Xiaofang Huo, Paul Yenerall, Amit Das, Shihong Ma, Ganesh V Raj, Ralf Kittler
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摘要

The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and metastatic PCa treatment. However, the occurrence of aberrant expression, mutated or splice variants of AR confers resistance to androgen ablation therapy (ADT), radiotherapy or chemotherapy in AR-positive PCa. Therapeutic strategies that effectively inhibit the expression and/or transcriptional activity of full-length AR, mutated AR and AR splice variants have remained elusive. In this study, we report that mithramycin (MTM), an antineoplastic antibiotic, suppresses cell proliferation and exhibits dual inhibitory effects on expression and transcriptio... More

关键词

Androgen receptor, Bleomycin, DNA damage Repair, Ionizing radiation, Mithramycin