Mechanisms of resistance to selective estrogen receptor down-regulator in metastatic breast cancer.
Based on the prominent role estrogen receptor (ER) plays in breast cancer, endocrine therapy has been developed to block the ER pathway and has shown great effectiveness. Fulvestrant, the first selective ER down-regulator (SERD), was demonstrated to completely suppress ERα and notably efficient. However, resistance to fulvestrant occurs, either intrinsic or acquired during the treatment. Several potential mechanisms inducing fulvestrant resistance have been proposed, composed of activated ERα-independent compensatory growth factor signaling, stimulated downstream kinases, altered cell cycle mediators, etcetera. Experimentally, combinations of fulvestrant with targeted treatments were reported to eliminate the resistance and improve the effect of fulvestrant. Meanwhile, some clinical trials associated with the targeted combination therapies are in progress. This review focuses on the underlying mechanisms that contribute to fulvestrant resistance in ER-positive breast cancer and provides an overview of combined fulvestrant with targeted agents to shed light on optimal therapies for patients with ER-positive breast cancer.
Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China.
Doudou
D
Huang
Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China.
Fang
F
Yang
Department of Oncology, Mayo Clinic, Rochester, MN, United States.
Yucai
Y
Wang
Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address: xguan@nju.edu.com.
Xiaoxiang
X
Guan
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen
Estrogen receptor-positive metastatic breast cancer; Fulvestrant resistance; Mechanism; Targeted combination therapy