Omics and therapy - a basis for precision medicine

Abstract

A founding premise of the human genome project was that knowledge of the spectrum of abnormalities that comprise cancers and other human diseases would lead to improved disease management by identifying molecular abnormalities that could guide disease detection and diagnosis, suggest new therapeutic strategies and be developed as markers to predict response to therapy. This project led to elucidation of a reference normal human genome sequence and normal polymorphisms therein against which sequences from diseased tissues can be compared to enable identification of causal abnormalities. It also stimulated development of an array of computational tools for genomic analysis and catalyzed public and private sector development of revolutionary tools for genome analysis that transformed analysis of whole genomes from an enterprise that required international teams and hundreds of millions of dollars to a process that can be carried out in core facilities for only a few thousand dollars per sample. Indeed, the $1000 genome is nearly upon us. Applications of these technologies to human cancers in international cancer genome projects are now revealing the spectra of abnormalities that comprise thousands of individual cancers. Analyses of these data are leading to the promised improvements in disease management. We review several aspects of cancer genomics with emphasis on aspects that are relevant to improving cancer therapy.

Figure 1

Omic endpoints to determine cancer subtypes. Tumors can be analyzed based on a variety of endpoints. The analyses can be used individually to stratify tumors into subtypes or in conjunction to further refine classification to determine appropriate targeted therapy in a highly specific manner.

Figure 2

Altered pathways in high‐grade serous ovarian carcinoma. Multiple genes in the Rb and PI3K/Ras pathways are mutated at varying frequencies. First published: Nature 2006.