From the Double Helix to Oncogenomics and Precision Cancer Medicine

Abstract

Abstract With the completion of the Human Genome Project in June 2000 and in step with the development of next generation -omics, a new era of medicine has started. In particular, the application and expansion of the molecular profiling of tumors have ushered in the development of personalized treatments, collectively referred to as precision cancer medicine (PCM), a field that is steadily growing. An increasing number of targetable molecules are being produced by the pharmaceutical industry, and their efficacy is strictly related to their specificity for reliable and well-characterized oncogenic pathways. The US Food and Drug Administration has therefore recommended that the development of these agents should be accompanied by companion diagnostics. The genomic revolution is also changing the way clinical trials of targeted drugs for cancer patients are being planned and conducted. The most common master protocols include basket trials, umbrella trials, and platform trials. Due to their flexibility and characteristics across molecularly defined tumor subtypes, novel drugs are included or excluded depending on their efficacy. Two examples on the use of precision diagnosis and treatment are described. The first one concerns patients with advanced non-small cell lung carcinoma, characterized by actionable or “druggable” oncogenic alterations and the sometimes remarkable improvement in objective response rates, progression-free survival, and overall survival compared with platinum-based chemotherapy. The second successful example of PCM is malignant melanoma. In parallel with a better understanding of the molecular mechanisms driving melanoma progression and drug resistance, the standard of care for this tumor has shifted from poorly effective chemotherapy to more optimistic targeted approaches. However, despite these encouraging results, a wider clinical application of PCM is still hampered by several drawbacks that will require major efforts before they can be overcome. It is hoped that, through the continuous and progressive refinement of its applications, PCM will eventually result in significant progress in the prevention, diagnosis, and treatment of tumors.