OCT 08, 2020 7:30 AM PDT

Keynote Presentation: RNA Splicing and Ancestry-related Molecular Targets in Precision Oncology and Cancer Disparities

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Deputy Director, Duke Cancer Institute, Professor of Medicine, Professor of Pharmacology and Cancer Biology, Professor of Family Medicine and Community Health, Duke University Medical Center
    Biography

      Steven R. Patierno, PhD serves as Professor of Medicine, Professor of Pharmacology and Cancer Biology and Professor of Family Medicine and Community Health at the Duke University School Medicine, and as Deputy Director of the Duke Cancer Institute (DCI), one of the original eight NCI-designated Comprehensive Cancer Centers. He earned a Bachelor of Science in Pharmacy from the University of Connecticut, a PhD in molecular pharmacology from the Graduate School of Biomedical Science, University of Texas Health Science Center-MD Anderson Cancer Institute in Houston Texas, and conducted an NIH-awarded postdoctoral fellowship at the University of Southern California (USC) Norris Comprehensive Cancer Center in molecular oncology and carcinogenesis. He was the Vivian Gill Distinguished Professor of Oncology, and Professor of Pharmacology, Physiology and Urology at the GWU School of Medicine and Health Sciences, and served as Executive Director of The George Washington University Cancer Center for ten years prior to moving to Duke in 2012. Dr. Patierno’s basic science and translational research laboratory has been funded continuously by the NIH, NCI, Department of Defense and multiple foundations for over 25 years. He is internationally recognized for research on molecular carcinogenesis, molecular pharmacology and oncology, the genomics of cancer disparities and healthcare delivery research on patient navigation and evidence-based policy. Currently, his laboratory is focused on the molecular biology of cancer disparities including the development of biomarkers for high risk cancer and identification and development of novel molecularly targeted therapeutics.  He serves on many national committees for AACR, AACI, and ASCO, and as chair of numerous scientific and medical advisory boards.  He co-chaired the 2007, and keynoted the 2018 AACR-NCI Think Tanks on Cancer Disparities and help found the AACR Science of Cancer Disparities Annual Conference. Dr. Patierno received a Prostate Cancer Foundation 2018 Challenge Award, the AACR 2019 Distinguished Cancer Disparities Research Award, and has been recognized as a Distinguished Alumnus of the University of Texas MD Anderson Cancer Institute.  He has also been recognized by Duke University for his extensive work in Diversity and Inclusion and by numerous organizations for impactful community engagement.


    Abstract

    Individuals of under-represented minority ancestry are at disproportional risk for higher incidence and mortality rates for particular cancers. The unequal burden of cancer in certain racial and ethnic groups, known as “cancer disparities”, can be attributed to a multilevel interplay among neighborhood and population-wide social, psychosocial, lifestyle, environmental, health system, and biological determinants of health. ARS is a key step in gene expression enabling individual genes to encode multiple proteins, and is emerging as a major driver of abnormal phenotypic heterogeneity including gaining aggressive characteristics and tolerance to anticancer therapy. RNA splicing–related genetic and genomic variation in tumors includes oncogenes dysregulated by ARS, spliceosome-dependent transformation, RNA splicing–related immunogenic epitopes and race–related cancer aggressiveness and drug response. Our laboratory has conducted a number of studies in multiple cancers stratified by race (both self-identified and by ancestral genotyping) using either deep RNAseq or array-based technologies on retro- and prospectively banked tissue samples, as well as computational analysis of publicly available databases such as TCGA. We have shown that the burden of race-related differential ARS (D-ARS) is much higher than differential gene expression, and that many of the D-ARS are functionally involved in oncogenic signaling pathways and statistically associate with survival. We have built an application, “CanSplice”, to mine genomic datasets for D-ARS by patient race and ethnicity. We have also begun to identify and test, preclinically and clinically, approaches to modulate and exploit ARS for therapeutic application, including splice-switching oligonucleotides, small molecules targeting RNA splicing or RNA splice variants, and combination regimens with immunotherapies. Our findings identify race-related ARS targets that may aid in the development of new biomarkers and precision therapeutic agents that have the potential to mitigate cancer disparities.

    Learning Objectives:

    1. Define the various contributors to cancer health disparities and some points of intersectionality between them

    2. Explain the potential role of RNA splicing in the biology of ancestry-related difference in the molecular etiology of cancer in different populations

    3. Identify approaches to pharmacologically target RNA splicing to mitigate cancer aggressiveness


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