Drugging the bad "AKT-TOR" to overcome TKI-resistant lung cancer.
EGFR kinase inhibitors constitute an important class of lung cancer treatments. While they produce dramatic responses in a subset of patients-primarily those with activating EGFR mutations-remissions are typically limited to several months due to acquired drug resistance, frequently associated with the secondary T790M mutation in EGFR. In this issue of Cancer Cell, Li et al. report that an irreversible EGFR kinase inhibitor, HKI-272, had limited activity in a mouse lung cancer model driven by an EGFR mutant harboring T790M and an activating mutation. However, combining HKI-272 with rapamycin promoted rapid tumor regression, suggesting a therapeutic strategy to overcome drug resistance.
Settleman
Jeffrey
J
Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA.
Kurie
Jonathan M
JM
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D051058:Oncogene Protein v-akt / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases