TY - JOUR
T1 - Cell Death Pathways in Lymphoid Malignancies
AU - Fletcher, Luke
AU - Nabrinsky, Edward
AU - Liu, Tingting
AU - Danilov, Alexey
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Purpose of Review: This review highlights the importance of the Bcl-2 family members in lymphoma cell survival and discusses the approaches to modulate their function, directly or indirectly, to advance lymphoma therapeutics. Recent Findings: The balance of cell death versus survival is ultimately leveraged at the mitochondria. Mitochondrial outer membrane permeabilization (MOMP) is the critical event that governs the release of pro-apoptotic molecules from the intermembrane mitochondrial space. MOMP is achieved through the coordinated actions of pro- and anti-apoptotic Bcl-2 family member proteins. Recognition of functional alterations among the Bcl-2 family member proteins led to identification of tractable targets to combat hematologic malignancies. Summary: A new class of drugs, termed BH3 mimetics, was introduced in the clinic. Venetoclax, a Bcl-2 inhibitor, received regulatory approvals in therapy of chronic lymphocytic leukemia and acute myeloid leukemia. Alternative pro-survival Bcl-2 family proteins, in particular Mcl-1, have been successfully targeted in preclinical studies using novel-specific BH3 mimetics. Finally, anti-apoptotic Bcl-2 family members may be targeted indirectly, via interference with the pro-survival signaling pathways, e.g., phosphoinotiside-3 kinase, B-cell receptor signaling, and NF-κB.
AB - Purpose of Review: This review highlights the importance of the Bcl-2 family members in lymphoma cell survival and discusses the approaches to modulate their function, directly or indirectly, to advance lymphoma therapeutics. Recent Findings: The balance of cell death versus survival is ultimately leveraged at the mitochondria. Mitochondrial outer membrane permeabilization (MOMP) is the critical event that governs the release of pro-apoptotic molecules from the intermembrane mitochondrial space. MOMP is achieved through the coordinated actions of pro- and anti-apoptotic Bcl-2 family member proteins. Recognition of functional alterations among the Bcl-2 family member proteins led to identification of tractable targets to combat hematologic malignancies. Summary: A new class of drugs, termed BH3 mimetics, was introduced in the clinic. Venetoclax, a Bcl-2 inhibitor, received regulatory approvals in therapy of chronic lymphocytic leukemia and acute myeloid leukemia. Alternative pro-survival Bcl-2 family proteins, in particular Mcl-1, have been successfully targeted in preclinical studies using novel-specific BH3 mimetics. Finally, anti-apoptotic Bcl-2 family members may be targeted indirectly, via interference with the pro-survival signaling pathways, e.g., phosphoinotiside-3 kinase, B-cell receptor signaling, and NF-κB.
KW - Apoptosis
KW - Bcl-2
KW - Mcl-1
KW - Venetoclax
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U2 - 10.1007/s11912-020-0874-3
DO - 10.1007/s11912-020-0874-3
M3 - Review article
C2 - 31989308
AN - SCOPUS:85078333163
SN - 1523-3790
VL - 22
JO - Current oncology reports
JF - Current oncology reports
IS - 1
M1 - 10
ER -