Targeted sequencing of pre-selected actionable genes is advocated for clinical application in terms of precision medicine or personalized therapy. Somatic mutation analysis is standard of practice for solid tumors to identify sensitizing and resistant mutations. Because many targeted agents in development are designed to counteract specific proteins and/or pathways commonly perturbed by tumor genetic changes, an urgent need exists to implement robust approaches that determine the “actionable” genetic profiles of individual tumors. These include the finite number of pre-specified hotspot mutations that can be assayed, which are designated a priori from a restricted subset of known cancer genes.
Arnedos et al. argued the concept of stratified medicine, i.e. developing one drug in a population for one recurrent genomic alternation which was clonally dominant, and the identification of promising genomic segments is the current model to develop precision medicine in (metastatic) breast cancer. In this presentation we will introduce the genomic alterations based on their clinical significance, as well as the definition of 4-tier classification of druggable targets. Two major references are: Li, Marilyn M. et al. (2017) “Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer” from the Journal of Molecular Diagnostics, Volume 19, Issue 1, 4 -23, and Mateo, J et al. (2018) “A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).” From the Annals of oncology vol. 29,9: 1895-1902.
Targeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients in terms of precision medicine. The critical point to the success of such approach is to standardize the guidelines for the interpretation and reporting of sequence variants in cancer, as discrepancy in functional annotation inevitably compromised the reproducibility and clinical implications of sequencing findings. |
