Tumor Heterogeneity and Therapeutic Resistance.

The rapidly changing landscape of oncology has brought new light, and with it, new challenges to optimizing therapeutic strategies for patients. Although the concept of patient heterogeneity is well known to any practicing clinician, a more detailed understanding of the biologic changes that underscore the clinical picture is beginning to emerge. Thus, tumor heterogeneity has come to encompass more than just the clinical picture and can represent both intratumor and intertumor differences. Within the fields of thoracic oncology and melanoma, the discovery of key molecular drivers has resulted in landmark breakthroughs in therapy. However, the complexities of tumor genetics and the interaction within the environment continue to drive the search for better therapies. Ongoing challenges include the accurate and timely assessment of genetic changes as well as the development of resistance and the resultant compensatory mechanisms. Novel technologies, including commercially available next-generation sequencing, have allowed for a greater breadth and depth of information to be gained from a single pathologic specimen, and it is now being incorporated into routine clinical practice. Translational advances have subsequently provided valuable insight into mechanisms of resistance, with the development of novel treatment strategies. Future work will focus on novel diagnostic techniques and adaptive mechanisms that can ultimately drive the development of the next generation of cancer therapy.