Diagnostic markers for treating cell proliferative disorders with telomerase inhibitors
Provided herein are methods for identifying individuals diagnosed with a cell proliferative disorder that will benefit from treatment with a telomerase inhibitor compound. Also provided herein are methods for treating these individuals with telomerase inhibitor compounds.
1. A method of detecting a relative telomere length in a sample from an individual diagnosed with or suspected of having a solid tumor cancer, the method comprising:
obtaining a formalin fixed paraffin embedded (FFPE) biological sample comprising cancer cells of a solid tumor from the individual;
analyzing the relative length of telomeric nucleic acids in cancer cells of the FFPE biological sample via quantitative PCR (qPCR) or telomere fluorescent in situ hybridization (telo-FISH) and determining whether the average relative telomere length in the cancer cells present in the FFPE biological sample from the individual is in the 50 th percentile or less of a relative telomere length range determined from one or more known standards selected from a telomere length range established from a plurality of naturally occurring tumors from a plurality of individuals diagnosed with the cancer and characterized cell lines.
2. The method of claim 1 , wherein the cancer is selected from lung cancer, breast cancer, liver cancer, ovarian cancer, gastric cancer, gastrointestinal cancer, gallbladder cancer, bladder cancer, glioblastoma, a sarcoma, melanoma, colorectal cancer and pancreatic cancer.
3. The method of claim 1 , wherein relative telomere length is determined by qPCR.
4. The method of claim 1 , wherein said one or more known standards are characterized cell lines.
5. The method of claim 1 , wherein said one or more known standards is from a plurality of naturally occurring tumors from a plurality of individuals.
6. The method of claim 2 , wherein the cancer is non-small cell lung cancer.
7. The method of claim 1 wherein the individual is a human.
8. The method of claim 4 , wherein the characterized cell lines are selected from the group consisting of: M14 cells, A549 cells, SK-5 cells, and Ovcar5 cells.
9. The method of claim 4 , wherein the characterized cell lines are selected from cell lines representative of the cancer cells present in the FFPE biological sample from the individual.
10. The method of claim 9 , wherein the characterized cell lines are non-small cell lung cancer cell lines, hepatocellular cell lines, or ovarian cell lines.
11. The method of claim 5 , wherein said cancer cells from the plurality of naturally occurring tumors are of the same type as the cancer cells present in the FFPE biological sample from the individual.
12. The method of claim 1 , wherein the average relative telomere length in the cancer cells present in the FFPE biological sample is determined to be in the 40th percentile, 35th percentile, 30th percentile, 25th percentile, 20th percentile, 15th percentile, 10th percentile, or 5th percentile or less of the relative telomere length range determined from the one or more known standards.
13. The method of claim 1 , wherein the relative telomere length is determined by telo-FISH.
14. The method of claim 13 , wherein the method further comprises deparaffinization of the FFPE biological sample.
15. The method of claim 3 , further comprising extracting the telomeric nucleic acids from the FFPE biological sample before determining relative telomere length.