Chapter 1 - Definition: Translational and Personalised Medicine, Biomarkers, Pharmacodynamics
Our understanding of the complex underlying mechanisms of cancer development and progression has improved with the application of novel laboratory-based techniques including DNA sequencing, gene expression profiling, analysis of DNA methylation, and proteomics. Following the publication of the first full-length human genome sequence in 2001, there have been many large-scale sequencing initiatives such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), projects that have characterised genomic alterations in solid tumours. These investigations have uncovered key mutations and molecular pathways involved in oncogenesis and cell proliferation that have an important impact on the diagnosis, prognosis, and treatment of patients and have enabled the tailoring of anti-cancer therapy in clinical practice. These discoveries also have important implications for individuals at high risk for developing certain solid tumours by identifying patients who may benefit from more intensive screening. For example, women with pathogenic germline mutations in the BRCA1 or BRCA2 tumour suppressor genes, involved in DNA repair of double-stranded breaks, are predisposed to developing breast, ovarian, and other cancers and are candidates for more specialised cancer screening programmes.
In addition to advances in molecular biology techniques, there have also been developments in diagnostic imaging and histopathology that have enabled more accurate diagnosis and characterisation of solid tumours and have provided for better monitoring of tumour response to treatment. For example, the development of fluorescence in situ hybridisation (FISH) techniques for use in the clinical laboratory has facilitated the routine testing of breast tumours for ERBB2 (HER2/neu) gene amplification in cases where immunohistochemistry staining is equivocal.
The identification of common genetic alterations in solid tumours, along with the development of high-throughput and cost-effective molecular diagnostics, is paving the way to enable the individualisation of cancer treatment.