Pathway-Directed Therapy in Multiple Myeloma

Cancers

MariaTheresa Krauth¹  Lukas John²  Marc-Steffen Raab²  Klaus Podar³ 

[1] Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria;Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany;Department of Internal Medicine, Karl Landsteiner University of Health Sciences, Mitterweg 10, 3500 Krems an der Donau, Austria;

关键词: multiple myeloma;    signaling pathways;    RAS/RAF/MEK/ERK-pathway;    PI3K/AKT-pathway;    BRAF;    mTOR;   

DOI  :  10.3390/cancers13071668

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown