Although c‑MYC contributes to tamoxifen resistance, it improves cisplatin sensitivity in ER‑positive breast cancer

尽管 c-MYC 导致他莫昔芬耐药,但它可以提高 ER 阳性乳腺癌对顺铂的敏感性

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作者:Rui Chen, Shipeng Guo, Chengcheng Yang, Lu Sun, Beige Zong, Kang Li, Li Liu, Gang Tu, Manran Liu, Shengchun Liu

Abstract

Tamoxifen (TAM) resistance is a major challenge in the treatment of estrogen receptor‑positive (ER+) breast cancer. To date, to the best of our knowledge, there are only a few studies available examining the response of patients with TAM‑resistant breast cancer to chemotherapy, and the guidelines do not specify recommended drugs for these patients. In the present study, TAM‑resistant cells were shown to exhibit increased proliferation and invasion compared with the parent cells, and the increased expression of c‑MYC was demonstrated to play an important role in TAM resistance. Furthermore, the TAM‑resistant cells were significantly more sensitive to cisplatin compared with the parent cells, and the silencing of c‑MYC expression desensitized the cells to cisplatin through the inhibition of the cell cycle. An increased c‑MYC expression was observed in 28 pairs of primary and metastatic tumors from patients treated with TAM, and the clinical remission rate of cisplatin‑based chemotherapy was significantly higher compared with other chemotherapy‑based regimens in 122 patients with TAM resistant breast cancer. Taken together, the data of the present study demonstrated that although c‑MYC was involved in TAM resistance, it increased the sensitivity of ER+ breast cancer to cisplatin. Thus, cisplatin may be a preferred chemotherapeutic agent for the treatment of patients with TAM‑resistant breast cancer, particularly in patients where the rapid control of disease progression is required.

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