Identification of LKB1 mutations as predictive biomarkers for susceptibility to TOR kinase inhibitors

摘要

The invention provides a TOR kinase inhibitor for use in a method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, wherein the method comprises administering the TOR kinase inhibitor to a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome characterized by a LKB1 gene or protein loss or mutation, relative to wild type, wherein the TOR kinase inhibitor is 1-ethyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one or a pharmaceutically acceptable salt, clathrate, solvate, stereoisomer, or tautomer thereof. The TOR kinase inhibitor can be used use in a method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, wherein the the TOR kinase inhibitor is administered in combination with one or more agents selected from 2-deoxyglucose, metformin, phenformin and pemetrexed. The TOR kinase inhibitor can further be used for predicting the likelihood of a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome being responsive to TOR kinase inhibitor therapy.