BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines

Delphine Merino; Gemma L. Kelly; Guillaume Lessene; Andrew H. Wei; Andrew W. Roberts; Andreas Strasser

doi:10.1016/j.ccell.2018.11.004

BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines

Delphine Merino, Gemma L. Kelly, Guillaume Lessene, Andrew H. Wei, Andrew W. Roberts, Andreas Strasser

Australian Centre for Blood Diseases

Research output: Contribution to journal › Review Article › Research › peer-review

235 Citations (Scopus)

Abstract

Defects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only proteins to kill cancer cells. The BCL-2 inhibitor venetoclax has been approved for treatment of refractory chronic lymphocytic leukemia and this drug and inhibitors of pro-survival MCL-1 and BCL-XL are being tested in diverse malignancies. Defects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only proteins to kill cancer cells. The BCL-2 inhibitor venetoclax has been approved for treatment of refractory chronic lymphocytic leukemia and this drug and inhibitors of pro-survival MCL-1 and BCL-XL are being tested in diverse malignancies.

Original language	English
Pages (from-to)	879-891
Number of pages	13
Journal	Cancer Cell
Volume	34
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2018.11.004
Publication status	Published - 10 Dec 2018

Keywords

apoptosis
BCL-2
BH3-mimetic drugs
BH3-only proteins
cancer
MCL-1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccell.2018.11.004

283146824-oaFinal published version, 2.08 MB

Cite this

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title = "BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines",

abstract = "Defects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only proteins to kill cancer cells. The BCL-2 inhibitor venetoclax has been approved for treatment of refractory chronic lymphocytic leukemia and this drug and inhibitors of pro-survival MCL-1 and BCL-XL are being tested in diverse malignancies. Defects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only proteins to kill cancer cells. The BCL-2 inhibitor venetoclax has been approved for treatment of refractory chronic lymphocytic leukemia and this drug and inhibitors of pro-survival MCL-1 and BCL-XL are being tested in diverse malignancies.",

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AU - Merino, Delphine

AU - Kelly, Gemma L.

AU - Lessene, Guillaume

AU - Wei, Andrew H.

AU - Roberts, Andrew W.

AU - Strasser, Andreas

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AB - Defects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only proteins to kill cancer cells. The BCL-2 inhibitor venetoclax has been approved for treatment of refractory chronic lymphocytic leukemia and this drug and inhibitors of pro-survival MCL-1 and BCL-XL are being tested in diverse malignancies. Defects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only proteins to kill cancer cells. The BCL-2 inhibitor venetoclax has been approved for treatment of refractory chronic lymphocytic leukemia and this drug and inhibitors of pro-survival MCL-1 and BCL-XL are being tested in diverse malignancies.

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BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Translational Research Program to Advance Clinical Outcomes in Acute Myeloid Leukaemia

Toward effective targeted therapies for Acute Myeloid Leukaemia (AML)

Cite this

BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Projects

Translational Research Program to Advance Clinical Outcomes in Acute Myeloid Leukaemia

Toward effective targeted therapies for Acute Myeloid Leukaemia (AML)

Cite this