A NEW THERAPEUTIC STRATEGY IN MULTIPLE MYELOMA BASED ON SMALL MOLECULES DIRECTED TO NOTCH PATHWAY

N. PLATONOVA, C. PARRAVICINI, L. PALAZZOLO, S. SAPORITI, M. COLOMBO, V. VALLELONGA, D. GIANNANDREA, D. GIANA, A. NERI, I. EBERINI, R. CHIARAMONTE

Article ID: 6462
Vol 32, Issue 4S1, 2018
DOI: https://doi.org/10.54517/jbrha6462
Received: 8 September 2018; Accepted: 8 September 2018; Available online: 8 September 2018; Issue release: 8 September 2018

Abstract

Multiple myeloma (MM) is the second most common hematological malignancy. Although clinicaladvances, it is still incurable disease, sustained by a tight interaction of malignant plasma cells withthe bone marrow (BM) microenvironment that promotes tumor growth, immunosuppression, drugresistance, neoangiogenesis and bone destruction. The oncogenic Notch signaling plays a crucial role inMM. In particular, aberrant Notch2 receptor activation and Jag1 and 2 ligands overexpression stimulateMM cells to establish pathological interactions with BM that trigger MM progression. Our previousdata showed that these effects can be interfered by knocking down of Jag1 and 2 expression. Indirectapproaches to inhibit Notch signaling are mainly based on inhibition of γ-Secretase that catalyzesNotch activation along with other several g-Secretase substrates. Moreover, inhibition of all four Notchreceptors is associated with a gut toxicity. This evidence prompted us to develop a therapeutic tool toselectively inhibit Notch2 signaling triggered by Jag1 and 2.



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Copyright (c) 2018 N. PLATONOVA, C. PARRAVICINI, L. PALAZZOLO, S. SAPORITI, M. COLOMBO, V. VALLELONGA, D. GIANNANDREA, D. GIANA, A. NERI, I. EBERINI, R. CHIARAMONTE




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