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Updated: Jun 11, 2025
09:12
Author Spotlight: Advancements in Hypoxia-Sensitive CAR-T Therapy for Enhanced Cancer Immunotherapy
Published on: June 14, 2024
830
Unlocking Apoptotic Pathways: Overcoming Tumor Resistance in CAR-T-Cell Therapy
Zhanna Zhang1, Manqi Su1, Panruo Jiang1
1Department of Hematology, Dongyang Hospital Affiliated to WenZhou Medical University, Jinhua, Zhejiang, China.
Cancer Medicine
|October 8, 2024
Summary
Chimeric antigen receptor (CAR)-T-cell therapy shows promise, but resistance is a challenge. This review explores strategies targeting apoptotic pathways to enhance CAR-T cell efficacy and overcome cancer resistance.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Chimeric antigen receptor (CAR)-T-cell therapy has revolutionized cancer treatment.
- Therapeutic resistance remains a significant hurdle, limiting patient outcomes.
Purpose of the Study:
- To review challenges in CAR-T-cell therapy.
- To focus on the role of apoptotic pathways in overcoming resistance.
Main Methods:
- Examining strategies to sensitize tumor cells to CAR-T-mediated apoptosis.
- Investigating combination therapies (BH3 mimetics, Mcl-1, IAP, HDAC inhibitors).
- Exploring novel CAR constructs and targeting the tumor microenvironment (TME).
Main Results:
- Inhibiting anti-apoptotic proteins enhances tumor cell apoptosis.
- Targeting extrinsic pathways increases death receptor expression.
- Novel CAR constructs and TME modulation can improve efficacy.
Conclusions:
- Enhancing tumor cell apoptosis and CAR-T cell cytotoxicity is key to improving outcomes.
- Targeting apoptotic proteins offers a novel strategy to overcome resistance.
- This review provides a foundation for optimizing CAR-T cell therapies.
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