Novel therapeutic strategies targeting resistance mechanisms in hematologic malignancies: from BCL2 inhibition to immunomodulatory approaches
Qianyu Han, Shasha Jiang, Jirui Chen, Lei Xue
TL;DR
This paper reviews new treatments for blood cancers that target resistance mechanisms, including BCL2 inhibitors and immunomodulatory therapies, to improve patient outcomes.
Contribution
The paper provides a comprehensive review of recent (2020–2025) therapeutic strategies targeting resistance in hematologic malignancies, emphasizing BCL2 inhibition and immunomodulatory approaches.
Findings
BCL2 inhibitors like venetoclax achieve high response rates in CLL and AML but face resistance via MCL1/BCL-XL upregulation.
Immunomodulatory therapies, including IMiDs and CAR-T cells, show up to 90% response rates in relapsed multiple myeloma.
Combining BCL2 inhibition with immunotherapy improves progression-free survival by 30%–40%.
Abstract
Hematologic malignancies, including chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM), are characterized by high relapse rates due to intrinsic and acquired drug resistance. Resistance mechanisms often involve dysregulation of apoptosis pathways, such as B-cell lymphoma 2 (BCL2) family overexpression, and immune evasion through microenvironment modulation. This review synthesizes recent advances (2020–2025) in therapeutic strategies targeting these mechanisms, focusing on BCL2 inhibition and immunomodulatory approaches to overcome resistance and improve outcomes. We systematically reviewed literature from PubMed, Nature, and other databases, emphasizing clinical trials, mechanistic studies, and emerging combinations published between 2020 and 2025. Main Findings: BCL2 inhibitors like venetoclax have achieved high…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsCAR-T cell therapy research · Acute Myeloid Leukemia Research · Chronic Myeloid Leukemia Treatments