Tamoxifen, as an essential therapeutic tool in the treatment of estrogen receptor-positive breast cancer, has been available for the past three decades and is currently being utilized as a chemo-preventive agent for patients at high risk for breast carcinoma. However, the induction of chemo-resistance during therapy has indicated a significant challenge with regards to this agent. Areas covered: This review enumerates the role of MUC1-C proto-oncogene in tamoxifen resistance and describes a number of signaling pathways by which MUC1-C would mediate the development of resistance. Finally, recent clinical studies conducted on the magnitude of MUC1 in inducing tamoxifen resistance are described. Expert commentary: Mucin 1, or MUC1, is aberrantly overexpressed on the entire tumor cell surface of most human cancers. Thus, it may result in the upregulation of several signaling pathways, such as growth cascades related to receptor tyrosine kinases (RTK), β-catenin and E-cadherin, as well as promoting gene transcription of Ras-related protein Rab-31 in order to mediate tumor growth control in response to tamoxifen. On the contrary, MUC1 suppresses apoptotic events, which in turn impresses upon cell fate. Also, it has been demonstrated that silencing MUC1-C proto-oncogene is associated with increased sensitivity to tamoxifen-induced growth inhibitors.

Background: Focus on application of non-ionizing, extremely low frequency magnetic elds (ELF-EMF) as an alternative approach for treating cancer is rapidly rising nowadays. Nevertheless, little is known about the underlying anti-tumoral mechanism of action of them.Methods: In the present study, for the rst time, we reported that along with apoptosis, 2 h/day exposure to 100 Hz, 1 mT ELF-EMF for a 5-day period, can induce necroptosis, a speci c type of programed necrotic cell death, by promoting RIPK1/RIPK3/MLKL pathway which may also be responsible for observed pro-in ammatory responses in vivo, evident from an increase in plasma levels of proin ammatory cytokines including TNF-α, IL-1β, IL-2, IL-6, IL-17A and IFN-γ. Alongside, 30-day exposure to this system could also signi cantly suppress tumor growth and expression of markers of tumor cell proliferation, angiogenesis, and metastasis, namely Ki-67, CD31, VEGFR2 and MMP-9.Results: The number of tumor in ltrating lymphocytes (TILs), especially CD8+ T h cells were signi cantly increased following exposure to ELF-EMF. Interestingly, pretreating cancer cells with N-acetyl cysteine, a free-radical scavenger, or verapamil, an L-type calcium channel blocker in vitro, could diminish observed necroptotic and apoptotic responses while pretreating with calcium chloride, could aggravate responses.Conclusions: Overall, results of present study demonstrated that along with apoptosis, necroptosis is also

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