Editorial: Twenty Years On from Sequencing the Human Genome, Personalized/Precision Oncology Prepares to Meet the Challenges of Checkpoint Inhibitor Therapy

On April 14, 2003, the International Human Genome Project was declared complete after identifying, mapping, and sequencing approximately 92% of the human genome. Significant genetic alterations have now been identified in most human cancers. Personalized, or precision, oncology involves molecular profiling of tumors to identify targetable alterations for drug treatments. T-cell responses to antigens, including tumor-associated antigens, are mediated by the interaction between stimulatory and inhibitory signaling molecules, known as immune checkpoints. Targets of inhibitory checkpoints include programmed death 1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Challenges of checkpoint inhibition therapy include the prevalence and severity of immune-related adverse events (irAEs) and the short duration of response. Also, the beneficial effects in patients with hematologic malignancies other than Hodgkin’s lymphoma remain limited. Checkpoint inhibitors are now integrated into standard-of-care for patients with several types of cancer. This Editorial aims to highlight the impact and challenges of checkpoint inhibitors in personalized/precision oncology and how molecular technologies may begin to address these challenges.