Compositions and methods for treating ras/mapk mutant lung cancer

The present invention features compositions and methods for typing an ALK-, BRAF-, EGFR-, NRAS-, or KRAS- or mutant lung cancer in a subject as a cancer sensitive or resistant to an ALK inhibitor, MEK inhibitor, BRAF inhibitor, or EGFR inhibitor, and related methods of treating such cancers. In particular embodiments, the present invention features compositions and methods for typing an ALK-, BRAF-, EGFR-, NRAS-, or KRAS-mutant lung cancer, determining whether a subject having an ALK-, BRAF-, EGFR-, NRAS-, or KRAS-mutant lung cancer is eligible for entry into a clinical trial for an ALK inhibitor, MEK inhibitor, BRAF inhibitor, or EGFR inhibitor, and monitoring effectiveness of treatment of an ALK-, BRAF-, EGFR-, NRAS-, or KRAS-mutant lung cancer. In some embodiments, the methods comprise measuring a level, copy number, or sequence of KEAP1 or NRF2 polynucleotide in a biological sample obtained from the subject relative to a reference level or sequence. The present invention also features compositions and methods for increasing sensitivity to an ALK inhibitor, MEK inhibitor, BRAF inhibitor, or EGFR inhibitor and treating an ALK-, BRAF-, EGFR-, NRAS-, or KRAS-mutant lung cancer.