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The BCL-2 arbiters of apoptosis and their growing role as cancer targets
Summary
This article explores the role of the BCL-2 family of proteins in apoptosis and cancer development, and discusses the potential of 'BH3 mimetic' drugs as a new weapon against cancer. It describes the interactions between BCL-2 family members that trigger apoptosis, and the potential of BH3 mimetics to advance cancer therapy. It also discusses the encouraging preclinical studies of BH3 mimetics that target other BCL-2 pro-survival members, particularly MCL-1. Conflict of interest statement and figures are also included.
Q&As
What role does impaired apoptosis play in cancer development?
Impaired apoptosis plays a central role in cancer development.
How has deepening understanding of the BCL-2 protein family driven the development of cancer drugs?
Deepening understanding of the BCL-2 protein family has driven the development of a new class of cancer drugs that target various pro-survival members by mimicking their natural inhibitors, the BH3-only proteins.
How have BH3 mimetic drugs proven successful in clinical trials?
BH3 mimetic drugs have proven successful in clinical trials of venetoclax/ABT-199, leading to its approval for a refractory form of chronic lymphocytic leukaemia and to scores of on-going trials for other malignancies.
How do pro-survival BCL-2 family members constrain the mitochondrial outer membrane to inhibit apoptosis?
Pro-survival BCL-2 family members constrain the mitochondrial outer membrane to inhibit apoptosis by forming a BH3/surface groove interaction.
What new weapons against cancer are being explored?
New weapons against cancer being explored include BH3 mimetic drugs that target other BCL-2 pro-survival members, particularly MCL-1.
AI Comments
👍 This article provides an incredibly detailed and comprehensive overview of the BCL-2 protein family and the growing role it plays as a cancer target.
👎 This article is very technical and dense, making it inaccessible for people without an extensive background in medical science.
AI Discussion
Me: It's about the BCL-2 family of proteins, which control cell death and apoptosis and how they are being used as targets for cancer treatments. It describes how their interactions with other proteins trigger apoptosis, and how BH3 mimetic drugs are being used to target pro-survival members of the family to treat various forms of cancer. It also talks about the success of venetoclax/ABT-199 in a form of chronic lymphocytic leukemia, and how other BH3 mimetic drugs may offer promise for cancers that are resistant to venetoclax.
Friend: That's really interesting. So, what are the implications of this article?
Me: The implications are that understanding the mechanisms of how the BCL-2 family affects cancer development and therapy could lead to more effective cancer treatments. It suggests that these BH3 mimetic drugs could be powerful new weapons in the fight against cancer, and that they may offer promise for cancers that are resistant to other treatments. It's also encouraging that venetoclax/ABT-199 has been approved for a form of chronic lymphocytic leukemia, and that there are a number of ongoing trials for other types of cancer.
Action items
- Research the BCL-2 protein family and its role in cancer development and therapy.
- Explore the potential of BH3 mimetic drugs to advance cancer therapy.
- Investigate the clinical trials of venetoclax/ABT-199 and other BH3 mimetics for cancer treatment.
Technical terms
- BCL-2
- B-cell lymphoma 2, a protein family that regulates apoptosis (programmed cell death)
- Apoptosis
- Programmed cell death
- BH3-only proteins
- Proteins that act as natural inhibitors of BCL-2
- BH3 mimetic drugs
- Drugs that mimic the action of BH3-only proteins
- Venetoclax/ABT-199
- A specific inhibitor of BCL-2
- MOM
- Mitochondrial outer membrane
- MCL-1
- A pro-survival member of the BCL-2 family