Methods to treat cancer with 10-propargyl-10-deazaaminopterin and methods for assessing cancer for increased sensitivity to 10-propargyl-10-deazaaminopterin

1. A method of selecting a patient for treatment of a cancer with 10-propargyl-10-deazaaminopterin, the method comprising the steps of:

(a) obtaining a sample of the patient's cancer tissue;

(b) determining the expression level of at least one selected polypeptide expressed in the sample;

(c) comparing the determined expression level in the sample with a reference expression level for the same at least one polypeptide; and

(d) selecting the patient for treatment 10-propargyl-10-deazaaminopterin where the comparison of the expression level in the sample of the at least one polypeptide and the corresponding reference expression levels indicate sensitivity to 10-propargyl-10-deazaaminopterin,

wherein the at least one selected polypeptide is selected from the group consisting of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), γ-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT).

2. The method of claim 1 , wherein the at least one selected polypeptide is RFC-1.

3. The method of claim 1 , wherein the at least one selected polypeptide is FPGS.

4. The method of claim 1 , wherein the at least one selected polypeptide is DHFR.

5. The method of claim 1 , wherein the patient's cancer is lymphoma, multiple myeloma, or NSCLC.

6. The method of claim 5 , wherein the lymphoma is a T-cell lymphoma selected from the group consisting of lymphoblastic lymphomas in which the malignancy occurs in primitive lymphoid progenitors from the thymus; mature or peripheral T-cell neoplasms, including T-cell prolymphocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK-cell leukemia, cutaneous T-cell lymphoma (Mycosis fungoides/Sezary syndrome), anaplastic large cell lymphoma, T-cell type, enteropathy-type T-cell lymphoma, Adult T-cell leukemia/lymphoma including those associated with HTLV-1, and angioimmunoblastic T-cell lymphoma, and subcutaneous panniculitic T-cell lymphoma; and peripheral T-cell lymphomas that initially involve a lymph node paracortex.

7. A method for assessing sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaaminopterin comprising the steps of:

(a) obtaining a sample of the patient's cancer tissue;

(b) determining the expression level of at least one selected polypeptide expressed in the sample;

(c) comparing the determined expression level in the sample with a reference expression level for the same at least one polypeptide to determine whether the reference expression level for a polypeptide is indicative for the expression level of that polypeptide in samples that are sensitive to 10-propargyl-10-deazaaminopterin; and

(d) generating a report of the sensitivity of the sample to 10-propargyl-10-deazaaminopterin,

wherein the at least one selected polypeptide is selected from the group consisting of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), γ-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT).

8. The method of claim 1 , wherein the cancer is a T-cell lymphoma, NSCLC, or multiple myeloma.

9. The method of claim 7 , wherein the at least one selected polypeptide is RFC-1.

10. The method of claim 7 , wherein the at least one selected polypeptide is FPGS.

11. The method of claim 7 , wherein the at least one selected polypeptide is DHFR.

12. The method of claim 7 , wherein the patient's cancer is lymphoma, NSCLC, or multiple myeloma.

13. The method of claim 12 , wherein the lymphoma is a T-cell lymphoma selected from the group consisting of lymphoblastic lymphomas in which the malignancy occurs in primitive lymphoid progenitors from the thymus; mature or peripheral T-cell neoplasms, including T-cell prolymphocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK-cell leukemia, cutaneous T-cell lymphoma (Mycosis fungoides/Sezary syndrome), anaplastic large cell lymphoma, T-cell type, enteropathy-type T-cell lymphoma, Adult T-cell leukemia/lymphoma including those associated with HTLV-1, and angioimmunoblastic T-cell lymphoma, and subcutaneous panniculitic T-cell lymphoma; and peripheral T-cell lymphomas that initially involve a lymph node paracortex.

14. A method for assessing sensitivity of a lymphoma to treatment with 10-propargyl-10-deazaaminopterin comprising the steps of

(a) obtaining a sample of the lymphoma;

(b) determining the amount of reduced folate carrier-1 enzyme (RFC-1) expressed by the sample, wherein higher levels of expressed RFC-1 are indicative of sensitivity to 10-propargyl-10-deazaaminopterin; and

(c) generating a report of the sensitivity of the sample to 10-propargyl-10-deazaaminopterin.

15. The method of claim 1 , wherein the at least one selected polypeptide is TS.

16. The method of claim 1 , wherein the at least one selected polypeptide is GGH.

17. The method of claim 1 , wherein the at least one selected polypeptide is GARFT.

18. The method of claim 7 , wherein the at least one selected polypeptide is TS.

19. The method of claim 7 , wherein the at least one selected polypeptide is GGH.

20. The method of claim 7 , wherein the at least one selected polypeptide is GARFT.