Computing the Cure: An Integrative Genomic Analysis to Directly Impact Patient Clinical Care

Cancer is a disease of the genome. Each cancer harbors its own unique set of somatic mutations, copy-number alterations, and epigenetic modifications that influence processes such as cell proliferation and survival. Although the presence of both inter- and intra-tumoral heterogeneity now is widely accepted, most malignant tumors still are treated with the oncologist having no knowledge of which mutations are present in the tumor and driving oncogenesis. When genetic testing is performed, only small sets of genes are analyzed, leaving the mutational status of the remaining 19,000-plus genes unknown. It has become increasingly obvious that knowledge of merely a handful of genes is insufficient to determine the best possible drug to eradicate a patient’s tumor. Rather, the doctor needs the full genomic context of mutations in addition to an interpretation of how the somatic alterations are functionally affecting the cancer in order to prescribe a drug that is likely to warrant a response. We have developed an integrative genomic approach to analyze individual tumors in order to recommend the appropriate therapy for a patient given their unique set of alterations. We analyze the full exome and transcriptome with next-generation sequencing, using our computational pipeline to extract clinically relevant mutations, copy-number alterations, and gene expression patterns of each tumor. Most importantly, we are able to complete this comprehensive analysis in a clinically relevant amount of time so it can be used to directly inform the patient’s course of treatment. The clinical utility of our approach is validated through the subsequent efficacy of treatments indicated by our analysis in each patient whose tumor is profiled.

Abstract Author(s): Aleah F. Caulin and the team at Cancer Therapeutics Innovation Group