Targeting BCL2 in Waldenström macroglobulinemia: from biology to treatment management DOI Creative Commons

Eleni Kalafati,

Efstathios Kastritis, Tina Bagratuni

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 22, 2025

Despite recent advances in the treatment of Waldenström macroglobulenimia (WM), including development Bruton tyrosine kinase inhibitors (BTKis), disease remains incurable highlighting urgent need for new treatments. The overexpression BCL2 WM cells promotes cell survival by resisting apoptosis and contributes to resistance chemotherapy targeted therapies. Concurrently, Bcl2 proteins that are encoded oncogenes supporting frequently upregulated WM, even presence DNA-damaging agents, hence have emerged as an alternative therapeutic target. Venetoclax serves a novel orally administered small agent targets Bcl-2 protein acting homology domain 3 (BH3) mimetic has shown promising results patients, those previously treated with BTKis. Furthermore, venetoclax, combination standard regimens, enhanced activity, but further studies required elucidate mechanism its synergistic action identify patients who can benefit from combined therapy. New advanced stages clinical may offer additional options. present review will focus on current knowledge we input these compounds “from bench bedside,” their utility managing relapsed/refractory patients.

Language: Английский

Targeting BCL2 in Waldenström macroglobulinemia: from biology to treatment management DOI Creative Commons

Eleni Kalafati,

Efstathios Kastritis, Tina Bagratuni

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 22, 2025

Despite recent advances in the treatment of Waldenström macroglobulenimia (WM), including development Bruton tyrosine kinase inhibitors (BTKis), disease remains incurable highlighting urgent need for new treatments. The overexpression BCL2 WM cells promotes cell survival by resisting apoptosis and contributes to resistance chemotherapy targeted therapies. Concurrently, Bcl2 proteins that are encoded oncogenes supporting frequently upregulated WM, even presence DNA-damaging agents, hence have emerged as an alternative therapeutic target. Venetoclax serves a novel orally administered small agent targets Bcl-2 protein acting homology domain 3 (BH3) mimetic has shown promising results patients, those previously treated with BTKis. Furthermore, venetoclax, combination standard regimens, enhanced activity, but further studies required elucidate mechanism its synergistic action identify patients who can benefit from combined therapy. New advanced stages clinical may offer additional options. present review will focus on current knowledge we input these compounds “from bench bedside,” their utility managing relapsed/refractory patients.

Language: Английский

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