Abstract

Translating Cancer Genomics to Medicine

Amit Dutt, Assistant Professor & Principal Investigator, Tata Memorial Centre

Recent developments in genomic research and targeted cancer therapy provide a unique opportunity to improve cancer care. The identification of inherited and somatic mutations in cancer has revealed key biological pathways that underlie the initiation and progression of cancer. In turn, these advances are beginning to transform diagnostics (allowing cancers to be classified based on molecular mechanism and allowing clinical trials to be undertaken on more homogeneous groups of patients) and therapeutics (sparking a new generation of drugs targeted at the molecular alterations that cause cancer). At the same time, these discoveries have underscored the complexity of cancer genetics; at present, we know only a subset of the genes that play a causal role in cancer. A comprehensive catalog of all such genetic lesions, together with a description of the cancer types in which they occur and the combinations in which they co-occur, is necessary for the effective development of targeted cancer therapy. However, despite much advances, it has not been technically feasible to interrogate the complete set of genomic alterations in a tumor in a systematic, comprehensive manner. This limitation is now set to change. Newer generation SNP arrays and massively parallel Next Generation DNA sequencing technologies already make possible the readout of millions and billions of nucleotides in a single run and will permit complete genome characterization of cancer. These methodologies and tools are been used to advance cancer sciences, leading to discovery of novel molecular subclasses, new therapeutic targets and biomarkers for clinical development. Using these and conventional technologies, our work led to the identification of causal alterations in human cancer and discovered novel somatic activating alterations at FGFR2, EGFR, AKT, PDGFRA and FGFR1 m