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Journal of Gastrointestinal & Digestive System | ISSN: 2161-069X | Volume: 8
&
&
October 29-30, 2018 | San Francisco, USA
International Conference on
Gastrointestinal Cancer and Therapeutics
4
th
World Congress on
Digestive & Metabolic Diseases
26
th
Annual Congress on
Cancer Science and Targeted Therapies
Testing HER2-related therapeutic strategies in GI cancers guided by integrated genomics
M
any somatic mutations have been detected in GI cancers, leading to the identification of some key drivers of disease
progression,buttheinvolvementoflargegenomicrearrangementshasoftenbeenoverlooked.Chromosomalrearrangement
detection allows coverage of the entire genome as opposed to narrowly focusing on selected genes. It is far less prone to false
positives and can potentially identify driving rearrangements/fusions within pathways that may be therapeutically targetable.
Due to tumor-specificity of the breakpoint-junctions, it can be used for defining clonal relationships and allows for designing
individualized diagnostic tests for monitoring a patient’s disease progression. We performed mate-pair sequencing (MPseq)
on genomic DNA and RNAseq on mRNA from several patients with pancreatic adenocarcinoma, cholangiocarcinoma and
colorectal cancer to identify genome-wide rearrangements. We found a small number of potentially targetable amplifications
and fusions including four cases with ERBB2 amplification. 3D micro cancer modeling was performed followed by a drug
screen informed by the genomic analysis. Finally, dose-response curves (including IC
50
values), were generated after measuring
cellular ATP. Significant responses were noted for all Her2 targeted therapies. The combined genomic/micro cancer analysis
pointed towards the possibility that these patients have a Her2 activated pathway and could benefit fromHer2 targeted therapies.
Biography
George Vasmatzis is a Consultant in the Department of Molecular Medicine and a member of the Mayo Clinic Cancer Center, as well as the co-director of the
Biomarker Discovery Program, within the Center for Individualized Medicine. His research program consists of bioinformatics specialists, molecular biologists,
epidemiologists, and pathologists. His team has demonstrated success in discovery and translation of several biomarkers as well as developing evidence-based
models that should help clinicians stratify (cancer) patients in order to provide each individual with the appropriate care. With the recent advances in Next Generation
Sequencing (NGS) technologies his laboratory has been engaging in massive sequencing to scan the genome of cancer cells for abnormalities that can be used for
clinical purposes such as diagnosis and stratification of patients for optimal treatment. Published papers in the journal of Clinical Oncology, Cancer Research, and
BLOOD further demonstrate their discovery, validation, and translation capabilities.
vasmatzis.george@mayo.eduGeorge Vasmatzis
Mayo Clinic, USA
George Vasmatzis, J Gastrointest Dig Syst 2018, Volume 8
DOI: 10.4172/2161-069X-C8-084