Integrating Genomics into Drug Discovery and Development: Challenges and Aspirations

Molecular biomarkers are increasingly being used to identify subgroups of patients that have a higher chance of benefiting from targeted therapies. Identification of predictive biomarkers and development of companion diagnostics to accompany targeted agents have been shown to significantly improve the efficacy and approval rate of these novel therapies, making treatment decisions more personalized to individual patients. Mutations of epidermal growth factor receptor (EGFR) and rearrangements of anaplastic lymphoma kinase (ALK) in non-small-cell lung cancer and of BRAF in melanoma provide great examples of driver mutations defining patient subgroups that respond to specific therapeutic agents. Recent advances in genomic technologies such as next-generation sequencing offer new opportunities for discovery and development of targeted therapies. They also pose numerous challenges in implementing molecularly guided precision medicine in clinical care. In this article, we review how molecular diagnostics have evolved over recent decades, discuss types and capabilities of clinically applicable genomic technologies, and highlight examples of companion diagnostics that have gained regulatory approval. Finally, we discuss technical and regulatory challenges associated with incorporating next-generation genomic technologies into clinical practice and consider potential ways to overcome these challenges to enable precision medicine.