{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:44:54Z","timestamp":1790844294632,"version":"4.1.0"},"reference-count":470,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm)"},{"name":"SIRIC-CURAMUS (INCA-DGOS-Inserm_12560)"},{"name":"Soci\u00e9t\u00e9 Fran\u00e7aise d\u2019H\u00e9matologie (SFH)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2019s 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\u2019s 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\u2013drug conjugates, antibody\u2013radioisotope 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.<\/jats:p>","DOI":"10.3390\/cancers14246026","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T02:51:56Z","timestamp":1670467916000},"page":"6026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Current Status of Novel Agents for the Treatment of B Cell Malignancies: What\u2019s Coming Next?"],"prefix":"10.3390","volume":"14","author":[{"given":"Mariana","family":"Tannoury","sequence":"first","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Inserm, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5744-5612","authenticated-orcid":false,"given":"Delphine","family":"Garnier","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Inserm, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3366-1628","authenticated-orcid":false,"given":"Santos A.","family":"Susin","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Inserm, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Bauvois","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Inserm, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bukowski, K., Kciuk, M., and Kontek, R. 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