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Dual Targeting of MCL1 and NOXA as Effective Strategy for Treatment of Mantle Cell Lymphoma

Elisabeth Höring, Arnau Montraveta, Simon Heine, Markus Kleih, Lea Schaaf, Matthias C Vöhringer, Anna Esteve-Arenys, Gael Roué, Dolors Colomer, Elias Campo, German Ott, Walter E Aulitzky, Heiko van der Kuip

Br J Haematol. 2017 May;177(4):557-561.

PMID: 28295185

Abstract:

Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA-dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP130793270 Orlistat Related Compound D Orlistat Related Compound D 130793-27-0 Price
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