Therapeutic agents and approaches in the age of personalized cancer care

Management of cancer patients has undergone a tremendous evolution, from an absence of hope to the promise that each patient could choose from a plethora of agents the one to which their particular tumor would respond; from a single option of a lifethreatening attempt at surgical excision to a combined approach of surgery, chemotherapy, targeted agents, radiation, and supportive care. This has come about as our understanding of cancer has evolved from a nebulous curse to an appreciation for the logical complexities that make up uncontrolled growth. And while there is still much to learn, we find ourselves in an exciting era where we have the blueprint of the entire genome, an ability to test the full spectrum of genetic perturbations in a patient, and technologies to allow development of an arsenal against of such defects. Herein we will describe many of the classes of agents that might allow such treatments, and the technologies that let us define a patient’s malignancy. Chemotherapy originated from the observation that World War I soldiers exposed to sulfur mustard gas developed pancytopenia. Charged with discovering potential therapeutic values to such toxins, Louis Goodman and Alfred Gilman designed nitrogen mustard, collaborated with thoracic surgeon Gustav Lindskog, and achieved a partial remission in a nonHodgin’s lymphoma patient(1). Similar trial and error experiments continued, with the only patient specific facets to therapy being observations of which cancer patients responded. As investigators gained a better understanding of the biologic processes driving cancer, advances in chemistry allowed generation of site-specific inhibitors, and technologic discoveries improved high-throughput analysis of thousands of compounds, it became possible to generate compounds against specific pathways. With completion of the human genome project and advancements in tumor analysis methods such as gene sequencing and microarrays, evaluation of patient-specific pathways has become possible. Improvements in trial design hope to marry the advancements in therapeutic agents and patient tumor profiling to complete the promise of patient-directed therapy.