Clinical Experience with Pro-Apoptotic Agents in Precision Cancer Therapies, Volume 1 Targeting Oncogenic Drivers and Signaling Pathways in Lymphoid Malignancies
- Author(s)
- Lew, Thomas E; Seymour, John F;
- Journal Title
- Precision Cancer Therapies
- Abstract
- BH3-mimetics are a novel drug class of small molecule inhibitors of BCL2 family proteins which restore apoptosis in malignant cells. The only currently approved BH3-mimetic, the selective BCL2 inhibitor venetoclax, is highly efficacious in chronic lymphocytic leukemia and has rapidly advanced to an approved standard of care in frontline and relapsed disease in combination with anti-CD20 monoclonal antibodies. Venetoclax is active in other B-cell malignancies, particularly mantle cell lymphoma and Waldenstrom's macroglobulinemia. Venetoclax-containing combination regimens in follicular lymphoma and aggressive B-cell neoplasms have shown some promise, but further studies are required to optimize dose and scheduling in combinations to mitigate increased myelosuppression, and to find validated biomarkers of venetoclax sensitivity. Tumor lysis syndrome and myelosuppression are the most common toxicities of venetoclax and are readily manageable with established protocols. Future research will focus on overcoming venetoclax resistance, targeting other BCL2 family members and the rational design of synergistic combinations.
- Publisher
- Wiley
- Keywords
- apoptosis; programmed cell death; BCL2; venetoclax; navitoclax; lymphoma; chronic lymphocytic leukemia; non-Hodgkin's lymphoma
- Research Division(s)
- Blood Cells And Blood Cancer
- Publisher's Version
- https://doi.org/10.1002/9781119819950.ch12
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-30 02:16:11
Last Modified: 2023-06-30 02:50:40