Synergistic Effects of PI3K and c-Myc Co-targeting in Acute Leukemia: Shedding New Light on Resistance to Selective PI3K- δ Inhibitor CAL-101.

Synergistic Effects of PI3K and c-Myc Co-targeting in Acute Leukemia: Shedding New Light on Resistance to Selective PI3K-δ Inhibitor CAL-101. Cancer Invest. 2019 Aug 14;:1-14 Authors: Riyahi N, Safaroghli-Azar A, Sheikh-Zeineddini N, Sayyadi M, Bashash D Abstract Enthusiasms into the application of PI3K-δ inhibitor CAL-101 has been muted due to the over-activation of compensatory molecules. Our results delineated that c-Myc suppression using 10058-F4 enhanced CAL-101 cytotoxicity in less sensitive cells through different mechanisms based on p53 status; while CAL-101-plus-10058-F4 induced G1 arrest in wild-type p53-expressing leukemic cells, no conspicuous increase in G1 was noted in U937 cells harboring mutant p53. Conclusively, this study shed lights on the role of c-Myc oncoprotein in acute leukemia cells sensitivity to PI3K inhibitor and outlined that the combination of c-Myc inhibitor and CAL-101 may be a promising therapeutic approach in leukemia. PMID: 31412710 [PubMed - as supplied by publisher]
Source: Cancer Investigation - Category: Cancer & Oncology Tags: Cancer Invest Source Type: research