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Volume 2, Issue 2 (Suppl)
Chronic Obstructive Pulmonary Diseases
ISSN: 2572-5548
Page 30
August 31-September 01, 2017 Brussels, Belgium
&
International Conference on
Chronic Diseases
6
th
International Conference on
Microbial Physiology and Genomics
conference
series
.com
CO-ORGANIZED EVENT
Targeting the cardiolipin biosynthetic machinery in KRAS-mutant pancreatic cancer: A search for
novel therapeutics
P
ancreatic cancer (PCa) has only 6-8% five-year survival rate kills as many as 53,000 Americans each year, and active-duty
military personnel and veterans are at a high risk for this fatal disease. Therapy is challenging due to substantial drug
resistance and lack of knowledge about how the Kirsten Rous Sarcoma (KRAS) oncogene mutated in 90% cases, affects PCa cell
biology. Our approach to address this knowledge gap is to identify synthetic lethal targets (SLTs). SLTs are non-KRAS pathway
proteins which when targeted by drugs will initiate apoptosis in the mutant but not the wild type KRAS cells. We hypothesize
that the enzymes that make and remodel the mitochondrial phospholipid cardiolipin (CL), cardiolipin synthase (CLS) and
tafazzin respectively, are SLTs for PCa. Reason is that suppressing these enzymes specifically in PCa cells with KRAS mutations
will compromise the mitochondria in these cells by depleting CL, which will induce apoptosis. We screened FDA-approved
drugs for their ability to cause apoptosis and suppress tafazzin and CLS expression in mutant but not wild type KRAS PCa cells
and identified the selective estrogen receptor modulator raloxifene as the prime candidate. Our objective is to use raloxifene
as a small molecule probe to investigate the involvement of tafazzin and CLS in maintaining and renewing mitochondria
in KRAS-mutant PCa cells. Aims of this study are to: Evaluate the effect of suppressing CLS and tafazzin on mitochondrial
viability and production; investigate the effect of CLS and tafazzin suppression on mitochondrial function in KRAS-PCa and;
determine the mechanism of raloxifene-mediated suppression of CLS and tafazzin. Our proposal delineates the regulation
of mitochondrial viability, production and function by mutant KRAS gene, while establishing CLS and tafazzin as SLTs and
raloxifene as a potential candidate drug for PCa therapy.
Biography
Ashim Malhotra serves as an Assistant Professor of Pharmacology at School of Pharmacy, Pacific University in Oregon. He is a Pharmacist and Expert in Mitochondrial
Pharmacology. He has served as a grant Reviewer for National Science Foundation (NSF) and private biomedical foundations in the United States. He has also served as
Chair of the national sub-committee on strategic planning for Biological Sciences Section of the American Association of Colleges of Pharmacy (AACP). During his career,
he has been felicitated with awards for teaching, service and scholarship including the American Society of Pharmacology and Experimental Therapeutics Pharmacology
Educators award in 2017, the 2016 Pacific University Junior Faculty Award, the 2016 AACP Teacher of the Year Award, and along with his colleagues, the 2014 AACP
Innovations in Teaching Award. Prior to joining Pacific University, he worked at the New York University School of Medicine for five years and the New York Methodist
Hospital for two years. He received his PhD in 2006 from St. John’s University in New York, USA.
ashim.malhotra@pacificu.eduAshimMalhotra
Pacific University Oregon, USA
Ashim Malhotra, Chron Obstruct Pulmon Dis 2017, 2:2
DOI: 10.21767/2572-5548-C1-001