Methods of diagnosing and prognosing lung cancer
The present invention provides methods of detecting cancer using biomarkers.
1. A method of treating a human subject with a non-small cell lung cancer (NSCLC), comprising:
providing an NSCLC sample obtained from the human subject;
detecting a level of Lkb1 activity in the human subject-derived NSCLC sample and a level of Lkb1 activity in a normal sample;
detecting activated K-ras in the human subject-derived NSCLC sample; and
administering an mTor inhibitor to the human subject if the level of Lkb1 activity in the subject-derived NSCLC sample is reduced compared to the level in the normal sample and activated K-ras is detected.
2. The method of claim 1 , wherein the subject-derived NSCLC sample is a tumor biopsy.
3. The method of claim 1 , wherein detecting the levels of Lkb1 activity in the human subject-derived NSCLC sample and the normal sample comprises detecting a level of Lkb1 nucleic acid or protein.
4. The method of claim 3 , wherein the level of Lkb1 protein is detected using an immunoassay.
5. The method of claim 3 , wherein the level of Lkb1 nucleic acid is detected using Northern hybridization analysis comprising at least one probe that binds to an Lkb1 sequence, or reverse transcriptase (RT)-PCR.
6. The method of claim 1 , wherein the level of Lkb1 activity is reduced when the level of Lkb1 nucleic acid or protein in the human subject-derived NSCLC sample is statistically significantly less than the level of nucleic acid or protein in the normal sample.
7. The method of claim 6 , wherein the level of Lkb1 nucleic acid or protein is statistically significantly less in the human subject-derived NSCLC sample when the probability that the difference in the levels of Lkb1 nucleic acid or protein between the two samples occurred by random chance is less than or equal to 0.05.
8. The method of claim 1 , wherein detecting the level of Lkb1 activity in the human subject-derived NSCLC sample comprises detecting a sequence of an Lkb1 nucleic acid in the subject-derived NSCLC sample.
9. The method of claim 8 , wherein the level of Lkb1 activity is reduced when the Lkb1 nucleic acid sequence comprises an inactivating mutation.
10. The method of claim 9 , wherein the inactivating mutation inactivates Lkb1 kinase activity.
11. The method of claim 9 , wherein the inactivating mutation comprises a disruption of the Lkb1 coding sequence, an insertion of one or more stop codons in the Lkb1 coding sequence, an insertion of a DNA fragment, a deletion of coding sequence or a substitution of a stop codon for coding sequence.
12. The method of claim 9 , wherein the inactivating mutation comprises a mutation at amino acid residue 78 of the Lkb1 protein.
13. The method of claim 1 , wherein the NSCLC is squamous carcinoma, large cell carcinoma, adenocarcinoma or a mixed tumor.
14. The method of claim 1 , wherein detecting the activation of K-ras comprises detecting one or more mutations in K-ras comprising a glycine to aspartic acid substitution at amino acid 12 of the K-ras protein (K-ras G12D ).
15. The method of claim 1 , wherein the mTor inhibitor is rapamycin.