Targeting oncogenic drivers

Cancer is a genetic disease caused by a series of somatic and/or germline mutations. The roles of oncogenes and tumor suppressors in cancer molecular origin have been well established. Targeting oncogene products has become an attractive therapeutic strategy with great clinical success, whereas tumor suppressors are considered 'undruggable' because current technology is not able to restore tumor suppressor function in metastatic disease. Although systematic approaches to discover genetic alterations have become available to individual patients, differentiating driver from passenger mutations and identifying and validating drug targets remain challenging. Protein tyrosine kinases play crucial roles in virtually all cellular processes and possess structural features that render them 'druggable'. Monoclonal antibodies and small-molecule inhibitors represent two major classes of targeted therapeutic agents, each possessing its own strength and weakness. Although initial successes have been achieved, targeted therapy faces many challenges that need to be addressed and hurdles to overcome.