title: Mapping the Pathways of Resistance to Targeted Therapies.
abstract: Resistance substantially limits the depth and duration of clinical responses to targeted anticancer therapies. Through the use of complementary experimental approaches, investigators have revealed that cancer cells can achieve resistance through adaptation or selection driven by specific genetic, epigenetic, or microenvironmental alterations. Ultimately, these diverse alterations often lead to the activation of signaling pathways that, when co-opted, enable cancer cells to survive drug treatments. Recently developed methods enable the direct and scalable identification of the signaling pathways capable of driving resistance in specific contexts. Using these methods, novel pathways of resistance to clinically approved drugs have been identified and validated. By combining systematic resistance pathway mapping methods with studies revealing biomarkers of specific resistance pathways and pharmacologic approaches to block these pathways, it may be possible to rationally construct drug combinations that yield more penetrant and lasting responses in patients.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina. kris.wood@duke.edu.
authors.forename: Kris C
authors.initials: KC
authors.lastname: Wood
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents