TY - JOUR
T1 - Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies
T2 - Current Overview in Cancer
AU - D'Aguanno, Simona
AU - Del Bufalo, Donatella
N1 - Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2020/5/21
Y1 - 2020/5/21
N2 - The dynamic interplay between pro-death and pro-survival Bcl-2 family proteins is responsible for a cell's fate. Due to the recognized relevance of this family in cancer progression and response to therapy, different efforts have made in recent years in order to develop small molecules able to target anti-apoptotic proteins such as Bcl-2, Bcl-xL and Mcl-1. The limitations of the first Bcl-2 family targeted drugs, regarding on-target and off-target toxicities, have been overcome with the development of venetoclax (ABT-199), the first BH3 mimetic inhibitor approved by the FDA. The purpose of this review is to discuss the state-of-the-art in the development of drugs targeting Bcl-2 anti-apoptotic proteins and to highlight the potential of their application as single agents or in combination for improving anti-cancer therapy, focusing in particular on solid tumors.
AB - The dynamic interplay between pro-death and pro-survival Bcl-2 family proteins is responsible for a cell's fate. Due to the recognized relevance of this family in cancer progression and response to therapy, different efforts have made in recent years in order to develop small molecules able to target anti-apoptotic proteins such as Bcl-2, Bcl-xL and Mcl-1. The limitations of the first Bcl-2 family targeted drugs, regarding on-target and off-target toxicities, have been overcome with the development of venetoclax (ABT-199), the first BH3 mimetic inhibitor approved by the FDA. The purpose of this review is to discuss the state-of-the-art in the development of drugs targeting Bcl-2 anti-apoptotic proteins and to highlight the potential of their application as single agents or in combination for improving anti-cancer therapy, focusing in particular on solid tumors.
KW - Bcl-2
KW - cancer
KW - inhibitors
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U2 - 10.3390/cells9051287
DO - 10.3390/cells9051287
M3 - Review article
C2 - 32455818
AN - SCOPUS:85085539458
VL - 9
JO - Cells
JF - Cells
SN - 2073-4409
IS - 5
ER -