Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?
Mariana TannouryDelphine GarnierSantos A SusinBrigitte BauvoisPublished in: Cancers (2022)
Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today's commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton's tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody-drug conjugates, antibody-radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders.
Keyphrases
- tyrosine kinase
- small molecule
- cancer therapy
- signaling pathway
- acute lymphoblastic leukemia
- drug discovery
- healthcare
- current status
- palliative care
- ejection fraction
- machine learning
- dendritic cells
- bone marrow
- chronic pain
- drug delivery
- combination therapy
- cell proliferation
- big data
- pi k akt
- prognostic factors
- induced apoptosis
- human immunodeficiency virus
- drug induced
- artificial intelligence
- chronic myeloid leukemia