Related Experiment Video
Updated: Jun 8, 2026
Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis
Published on: January 26, 2024
Targeting survival pathways in lymphoma
Luca Paoluzzi1, Owen A O'Connor
1Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, The New York Presbyterian Hospital, Columbia University, New York, USA.
Abstract:
Targeting cellular death pathways including apoptosis is a promising strategy for cancer drug discovery. To date at least three major types of cell death have been distinguished, including: apoptosis, autophagy, and necrosis. Increasing evidence has begun to support a role of Bcl-2-family members in the cellular pathways involved in each of these processes. The induction of apoptosis in different types of tissue and in response to various stressors is a complex process that is controlled by different BCL-2 family members. Pharmacologic modulation of BCL-2 proteins and apoptosis can be achieved through different ways including the use of: (1) Modified peptides; (2) Small molecule inhibitors ofanti-apoptotic proteins; (3) Antisense strategies; and (4) TRAIL targeting. Non-peptide based small-molecule inhibitors of signaling pathways are at present the strategy of choice given their low antigenicity and generally more favorable pharmacokinetic and pharmacodynamic features, especially as they pertain to volume of distribution and intracellular accumulation. Bcl2-family inhibitors are showing impressive preclinical efficacy in animal models and are moving rapidly towards phase I and II clinical trials. Appropriate preclinical studies will need to identify the optimal strategies for combining these agents, with an emphasis on the importance of dose and schedule dependency.
Insights
Targeting cancer cell death pathways, like apoptosis, is key for drug discovery. Bcl-2-family inhibitors show promise, with small molecules being the preferred strategy due to favorable drug properties.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cellular death pathways, including apoptosis, autophagy, and necrosis, are crucial in cancer drug discovery.
- Bcl-2 family proteins play a significant role in regulating these cell death processes.
- Targeting apoptosis offers a promising therapeutic strategy for various cancers.
Purpose of the Study:
- To review the role of Bcl-2 family members in cellular death pathways.
- To discuss pharmacologic strategies for modulating BCL-2 proteins and apoptosis.
- To highlight the advantages of small-molecule inhibitors in cancer therapy.
Main Methods:
- Review of existing literature on Bcl-2 family proteins and apoptosis.
- Analysis of different pharmacologic approaches: modified peptides, small molecule inhibitors, antisense strategies, and TRAIL targeting.
- Evaluation of preclinical efficacy and clinical trial progression of Bcl-2 family inhibitors.
Main Results:
- Bcl-2 family members are implicated in apoptosis, autophagy, and necrosis.
- Small-molecule inhibitors of anti-apoptotic proteins are favored due to favorable pharmacokinetic and pharmacodynamic profiles.
- Bcl-2 inhibitors demonstrate significant preclinical efficacy and are advancing to clinical trials.
Conclusions:
- Targeting apoptosis via Bcl-2 family inhibitors is a viable cancer drug discovery strategy.
- Small-molecule inhibitors represent a promising therapeutic approach with favorable drug-like properties.
- Further preclinical studies are essential to optimize combination strategies, dose, and scheduling for Bcl-2 inhibitors.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
01:31The Intrinsic Apoptotic Pathway
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...