GENETIC PROFILING AND PERSONALIZED MEDICINE
Development of molecularly targeted cancer therapies opens the possibility that treatment could be tailored to the specific defect in the cancer of an individual patient. Such a personalized approach to cancer therapy has become feasible with recent technologic advances in DNA sequencing that allow mutational profiles of individual tumours to be determined over a short time interval. Technologies currently under development include array-based platforms for analysis of mutations in genes of interest, deep sequencing of known drivers of tumorigenesis (i.e., repeated reads of the sequence of interest), and whole genome or exome sequencing. Each approach has its advantages and disadvantages. For example, deep sequencing can identify mutations in subpopulations of cells that may be missed by other methods, but this approach is more costly and time-consuming. Approaches that rapidly test a limited number of genes, on the other hand, may miss changes that would be identified in whole genome/exome sequencing. Thus, the best strategy for personalized medicine remains to be determined. Because the analysis is normally performed on biopsies of primary tumours, the problem of regional heterogeneity in tumours and potential genetic differences in metastases also needs to be addressed for successful implementation of more personalized treatments.
Genetic profiling of tumours can also be used to gain prognostic information. Our increasing knowledge of the biology and genetics of cancer has led to the development of mutation and expression signatures that are associated with various cancer phenotypes. As a result, several commercial tests that use the mutational status of a panel of genes to predict the risk of recurrence and/or aggressiveness for breast (e.g., MammaPrint, Oncotype DX), colon (e.g., Oncotype DX), and prostate (e.g., Prolaris, Oncotype DX) cancers are now available for use in the clinical setting.