Progress in the Understanding of the Mechanism of Tamoxifen Resistance in Breast Cancer

Abstract

Tamoxifen is a drug commonly used in the treatment of breast cancer, especially for postmenopausal patients. However, its efficacy is limited by the development of drug resistance. Downregulation of estrogen receptor alpha (ERα) is an important mechanism of tamoxifen resistance. In recent years, with progress in research into the protective autophagy of drug-resistant cells and cell cycle regulators, major breakthroughs have been made in research on tamoxifen resistance. For a better understanding of the mechanism of tamoxifen resistance, protective autophagy, cell cycle regulators, and some transcription factors and enzymes regulating the expression of the estrogen receptor are summarized in this review. In addition, recent progress in reducing resistance to tamoxifen is reviewed. Finally, we discuss the possible research directions into tamoxifen resistance in the future to provide assistance for the clinical treatment of breast cancer.

The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer

“…Patients that are overexpressing HER2 are frequently treated with Trastuzumab (an humanized monoclonal antibody against this receptor) or, in most cases upon recurrence, lapatinib (an small molecular inhibitor of HER2 tyrosine kinase activity) [ 10 ]. Despite the implementation of these selective therapies against luminal and HER2 positive breast cancers, approximately 20–30% of the patients that are treated with endocrine therapy and 70% of patients that are treated with Trastuzumab develop resistance, and progress to a more advanced disease [ 11 ]. It is, therefore, essential to identify novel biomarkers that help to predict the acquisition of resistance to these therapies and to anticipate the progression of the disease to improve the management of patients with invasive luminal breast cancer.…”

Nuclear Receptor-Mediated Metabolic Reprogramming and the Impact on HR+ Breast Cancer

“…As cells shift from normal to hypoxic conditions, activation of HIF1α and its cofactor CBP/p300 cooperate to transcriptionally activate down-stream signaling that contributes to cell proliferation, glucose metabolism and chemotherapeutic resistance [ 210 ]. Consistent with these findings, estrogen dependent activation of HIF1α is associated with poor patient response and therapeutic resistance in ER+ tumors [ 211 , 212 , 213 , 214 , 215 , 216 ].…”

A Patent Review on the Current Developments of Benzoxazoles in Drug Discovery

“…It is involved in cell proliferation, cell growth, cell size, survival, motility, metabolism, and angiogenesis [82,83] . Resistance against some antitumour and anticancer drugs, such as tamoxifen [84] and letrozole, [85] is attributed to the activation of this pathway [86] . Hence, inhibition of this signalling pathway has been identified as a potential approach for developing targeted anticancer drugs [87] …”