To describe the emergence of targeted therapies that have led to significant breakthroughs in cancer therapy and completed or ongoing clinical trials of novel agents for the treatment of patients with advanced cancer.

The literature was systematically reviewed, based on clinical experience and the use of technologies that improved our understanding of carcinogenesis.

Genomics and model systems have enabled the validation of novel therapeutic strategies. Tumor molecular profiling has enabled the reclassification of cancer and elucidated some mechanisms of disease progression or resistance to treatment, the heterogeneity between primary and metastatic tumors, and the dynamic changes of tumor molecular profiling over time. Despite the notable technologic advances, there is a gap between the plethora of preclinical data and the lack of effective therapies, which is attributed to suboptimal drug development for “driver” alterations of human cancer, the high cost of clinical trials and available drugs, and limited access of patients to clinical trials. Bioinformatic analyses of complex data to characterize tumor biology, function, and the dynamic tumor changes in time and space may improve cancer diagnosis. The application of discoveries in cancer biology in clinic holds the promise to improve the clinical outcomes in a large scale of patients with cancer. Increased harmonization between discoveries, policies, and practices will expedite the development of anticancer drugs and will accelerate the implementation of precision medicine.

Combinations of targeted, immunomodulating, antiangiogenic, or chemotherapeutic agents are in clinical development. Innovative adaptive study design is used to expedite effective drug development.