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Pathway-directed therapy in multiple myeloma

Multiple Myeloma (MM) is a malignant plasma cell disorder with an unmet medical need, in particular for relapsed and refractory patients. Molecules within deregulated signaling pathways, including the RAS/RAF/MEK/ERK, but also the PI3K/AKT-pathway belong to the most promising evolving therapeutic ta...

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Bibliographic Details
Main Authors: John, Lukas (Author) , Krauth, Maria Theresa (Author) , Podar, Klaus (Author) , Raab, Marc-Steffen (Author)
Format: Article (Journal)
Language:English
Published: 1 April 2021
In: Cancers
Year: 2021, Volume: 13, Issue: 7, Pages: 1-19
ISSN:2072-6694
DOI:10.3390/cancers13071668
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers13071668
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/13/7/1668
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Author Notes:Lukas John, Maria Theresa Krauth, Klaus Podar and Marc-Steffen Raab

MARC

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520 |a Multiple Myeloma (MM) is a malignant plasma cell disorder with an unmet medical need, in particular for relapsed and refractory patients. Molecules within deregulated signaling pathways, including the RAS/RAF/MEK/ERK, but also the PI3K/AKT-pathway belong to the most promising evolving therapeutic targets. Rationally derived compounds hold great therapeutic promise to target tumor-specific abnormalities rather than general MM-associated vulnerabilities. This paradigm is probably best depicted by targeting mutated BRAF: while well-tolerated, remarkable responses have been achieved in selected patients by inhibition of BRAFV600E alone or in combination with MEK. Targeting of AKT has also shown promising results in a subset of patients as monotherapy or to resensitize MM-cells to conventional treatment. Approaches to target transcription factors, convergence points of signaling cascades such as p53 or c-MYC, are emerging as yet another exciting strategy for pathway-directed therapy. Informed by our increasing knowledge on the impact of signaling pathways in MM pathophysiology, rationally derived Precision-Medicine trials are ongoing. Their results are likely to once more fundamentally change treatment strategies in MM. 
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