Personalized cancer therapy with selective kinase inhibitors: an emerging paradigm in medical oncology.
Selective kinase inhibitors have emerged as an important class of anticancer agents, with demonstrated clinical efficacy and generally favorable toxicity profiles in several common disease settings where conventional treatments have previously provided only modest benefit. Consequently, a substantial effort is now underway to identify additional therapeutically relevant kinase targets and to develop and test inhibitors of those proteins in a variety of human malignancies. However, it has also become clear that the clinical benefit associated with these agents is typically limited to a subset of treated patients, who in many cases are defined by a specific genomic lesion within their tumor cells--frequently, an activating mutation within the gene encoding the target kinase. This discovery has prompted efforts to stratify patients before treatment with kinase inhibitors based on specific genomic biomarkers, with the goal of optimizing clinical outcomes through the effective personalization of treatment (ie, matching the right patients with the right therapies). With recent advances in our understanding of the relationship between tumor genotypes and cancer cell sensitivity to kinase inhibition, together with improved technologies for rapidly genotyping tumor biopsies for relevant lesions, the implementation of personalized cancer care with this exciting new class of inhibitors is now becoming a reality. In this review, we summarize recent developments in this area, and we highlight some of the logistical challenges posed by this emerging paradigm in medical oncology.
McDermott
Ultan
U
Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Settleman
Jeff
J
D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005544:Forecasting; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D015894:Genome, Human / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008495:Medical Oncology / Q000592:standards / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D018579:Patient Selection; D010597:Pharmacogenetics; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors