Health Care : Current Reviews

New opportunities in hematologic malignancy treatment: Therapeutic application of PI3K inhibitors

Joint Event on International Conference on Applied Microbiology and Microbial Biotechnology & International Conference on Microbiome R&D and Biostimulants & 3^rd International Conference on Internal Medicine & Hospital Medicine

October 15-16, 2018 Ottawa, Canada

Davood Bashash

Shahid Beheshti University of Medical Sciences, Iran

Posters & Accepted Abstracts: Health Care Current Reviews

Abstract:

Field of Research: Targeted therapy in cancer Statement of the Problem: Among signaling pathways involved in the pathogenesis of hematologic malignancies, constitutive activation of phosphatidylinositol 3-kinase (PI3K) has been observed in a high proportion of patients, largely as a result of genetic mutation. Here, we have evaluated and compared the effects of two different classes of PI3K inhibitors, which are currently being tested in clinical trials. Methodology: To define the effect of the isoform-specific PI3K? inhibitor CAL-101 and pan-PI3K inhibitor BKM120 in different types of hematologic malignancies, a panel of cell lines consists of multiple myeloma, acute lymphoblastic leukemia, and acute myeloblastic leukemia were chosen. Cell viability, apoptosis and caspase-3 activity were determined during incubation with either the inhibitors. The molecular mechanism was also evaluated by RQ-PCR and western blot analysis. Findings: Our results showed that both BKM120 and CAL-101 effectively reduced the cell viability of all malignant cells, independent of the mutational status of PTEN and p53, by causing cell cycle arrest and promoting ROS-mediated apoptosis. Despite favorable cytotoxic effects, we found remarkable differences in the ability of CAL-101 and BKM120. As compared to CAL-101, lower concentrations of BKM120 blocked Akt phosphorylation and caused a more pronounced apoptosis through both p53- and NF-?Bdependent pathways; suggesting that probably complete inhibition of class I PI3K isoforms more effectively abrogates leukemic cell proliferation and survival. Conclusion & Significance: Our data indicate a potential application for PI3K inhibitors in the treatment of hematologic malignancies, irrespective of the adverse prognostic markers, and support the clinical application of these inhibitors for patients.

Biography :

E-mail: d.bashash@sbmu.ac.ir