PMID- 36374739
OWN - NLM
STAT- MEDLINE
DCOM- 20221129
LR  - 20221129
IS  - 1879-0461 (Electronic)
IS  - 1040-8428 (Linking)
VI  - 180
DP  - 2022 Dec
TI  - New steps on an old path: Novel estrogen receptor inhibitors in breast cancer.
PG  - 103861
LID - S1040-8428(22)00285-2 [pii]
LID - 10.1016/j.critrevonc.2022.103861 [doi]
AB  - Estrogen receptor (ER) signaling represents the main driver of tumor growth and 
      survival in hormone receptor positive (HR+) breast cancer (BC). Thus, endocrine 
      therapy (ET) alone or in combination with targeted agents constitutes the 
      mainstay of the treatment for this BC subtype. Despite its efficacy, intrinsic or 
      acquired resistance to ET occurs in a large proportion of cases, mainly due to 
      aberrant activation of ER signaling (i.e. through ligand-independent ER 
      activation, in the presence of estrogen receptor 1 (ESR1) gene aberration or ER 
      protein phosphorylation) and/or the upregulation of escape pathways, such as the 
      PI3K/AKT/mTOR pathway. Therefore, the development of new ER pathway targeting 
      agents remains essential to delay and overcome ET resistance, enhance treatment 
      efficacy and tolerability, and ultimately prolong patient survival and improve 
      their quality of life. Several novel ER targeting agents are currently under 
      investigation. Among these, the oral selective ER degraders (SERDs) represent the 
      pharmacological class at the most advanced stage of development and promise to 
      enrich the therapeutic armamentarium of HR+ BC in the next few years, as they 
      showed promising results in several clinical trials, either as single ET agents 
      or in combination with targeted therapies. In this manuscript, we aim to provide 
      a comprehensive overview on the clinical development of novel ER targeting 
      agents, reporting the most up-to-date evidence on oral SERDs and other compounds, 
      including new selective ER modulators (SERMs), ER proteolysis targeting chimera 
      (PROTACs), selective ER covalent antagonists (SERCAs), complete ER antagonists 
      (CERANs), selective human ER partial agonists (ShERPAs). Furthermore, we discuss 
      the potential implications of introducing these novel treatment strategies in the 
      evolving and complex therapeutic scenario of HR+ BC.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Pagliuca, Martina
AU  - Pagliuca M
AD  - Department of Clinical Medicine and Surgery, University Federico II, Naples, 
      Italy; Gustave Roussy, University Paris Saclay, Villejuif, France.
FAU - Donato, Marco
AU  - Donato M
AD  - Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, 
      Italy.
FAU - D'Amato, Agostina Lagodin
AU  - D'Amato AL
AD  - Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS Ospedale 
      Policlinico San Martino, Genova, Italy.
FAU - Rosanova, Mario
AU  - Rosanova M
AD  - Oncology Unit, Ospedale del Mare, Naples, Italy.
FAU - Russo, Anna Orsola Maria
AU  - Russo AOM
AD  - U.O. Oncologia Medica P.O. Ospedale delle Murge F. Perinei, Altamura, Italy.
FAU - Scafetta, Roberta
AU  - Scafetta R
AD  - Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, 
      Italy.
FAU - De Angelis, Carmine
AU  - De Angelis C
AD  - Department of Clinical Medicine and Surgery, University Federico II, Naples, 
      Italy.
FAU - Trivedi, Meghna V
AU  - Trivedi MV
AD  - Department of Pharmacy Practice and Translational Research, University of Houston 
      College of Pharmacy, Houston, TX, USA.
FAU - Andre, Fabrice
AU  - Andre F
AD  - Gustave Roussy, University Paris Saclay, Villejuif, France.
FAU - Arpino, Grazia
AU  - Arpino G
AD  - Department of Clinical Medicine and Surgery, University Federico II, Naples, 
      Italy.
FAU - Del Mastro, Lucia
AU  - Del Mastro L
AD  - Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS Ospedale 
      Policlinico San Martino, Genova, Italy.
FAU - De Laurentiis, Michelino
AU  - De Laurentiis M
AD  - National Cancer Institute IRCCS - Fondazione G. Pascale, Naples, Italy.
FAU - Puglisi, Fabio
AU  - Puglisi F
AD  - Department of Medicine, University of Udine, Udine, Italy; Department of Medical 
      Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy.
FAU - Giuliano, Mario
AU  - Giuliano M
AD  - Department of Clinical Medicine and Surgery, University Federico II, Naples, 
      Italy. Electronic address: m.giuliano@unina.it.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20221028
PL  - Netherlands
TA  - Crit Rev Oncol Hematol
JT  - Critical reviews in oncology/hematology
JID - 8916049
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (Selective Estrogen Receptor Modulators)
RN  - 0 (Estrogens)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Receptors, Estrogen/metabolism
MH  - *Breast Neoplasms/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Quality of Life
MH  - Selective Estrogen Receptor Modulators/therapeutic use
MH  - Estrogens/therapeutic use
OTO - NOTNLM
OT  - ER signaling
OT  - Endocrine resistance
OT  - PROTACs
OT  - SERCAs
OT  - SERDs
EDAT- 2022/11/15 06:00
MHDA- 2022/11/30 06:00
CRDT- 2022/11/14 13:37
PHST- 2022/10/13 00:00 [received]
PHST- 2022/10/25 00:00 [revised]
PHST- 2022/10/25 00:00 [accepted]
PHST- 2022/11/15 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/11/14 13:37 [entrez]
AID - S1040-8428(22)00285-2 [pii]
AID - 10.1016/j.critrevonc.2022.103861 [doi]
PST - ppublish
SO  - Crit Rev Oncol Hematol. 2022 Dec;180:103861. doi: 
      10.1016/j.critrevonc.2022.103861. Epub 2022 Oct 28.