Targeting tumors that lack methylthioadenosine phosphorylase (MTAP) activity: Current strategies

Cancer Biology and Therapy

Volumn 11, Issue 7, 2011, Pages 627-632

  Bertino, Joseph R ^a   Waud, William R ^b   Parker, William B ^b   Lubin, Martin ^c  

^a ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^b SOUTHERN RESEARCH INSTITUTE   (United States)

^c DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

6 mercaptopurine; Adenine; Methotrexate; MTA; MTAP

Indexed keywords

2 FLUOROADENINE; 2,6 DIAMINOPURINE; 5' METHYLTHIOADENOSINE; 5' METHYLTHIOADENOSINE PHOSPHORYLASE; 5,10 DIDEAZAFOLATE; 6 METHYLPURINE; ADENINE DERIVATIVE; ALANOSINE; ALANOSINYL 5 AMINO 4 IMIDAZOLE CARBOXYLIC ACID RIBONUCLEOTIDE; AZASERINE; CARBOXYLIC ACID DERIVATIVE; CISPLATIN; FLUOROURACIL; FOLIC ACID ANTAGONIST; FOLIC ACID DERIVATIVE; HYPOXANTHINE; MERCAPTOPURINE; METHOTREXATE; NUCLEOTIDE; PEMETREXED; PURINE DERIVATIVE; PYRIMIDINE DERIVATIVE; TIOGUANINE; UNCLASSIFIED DRUG;

ACUTE LYMPHOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; CANCER COMBINATION CHEMOTHERAPY; CELL KILLING; CELL PROLIFERATION; CLINICAL TRIAL (TOPIC); COLON CANCER; CONTINUOUS INFUSION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG INHIBITION; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG SENSITIVITY; DRUG SYNTHESIS; ENZYME ACTIVITY; GENE EXPRESSION; GENE FREQUENCY; GENE TARGETING; HOST CELL; HUMAN; IMMUNOHISTOCHEMISTRY; LEUKEMIA; LUNG NON SMALL CELL CANCER; LYMPHOMA; MAXIMUM TOLERATED DOSE; MELANOMA; MESOTHELIOMA; MULTIPLE CYCLE TREATMENT; NONHUMAN; OSTEOSARCOMA; PANCREAS CANCER; REVIEW; SOFT TISSUE SARCOMA; SOLID TUMOR; T CELL LYMPHOMA; TREATMENT RESPONSE; TUMOR CELL; TUMOR GROWTH;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PURINE-NUCLEOSIDE PHOSPHORYLASE; PURINES;

EID: 79953319582     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.11.7.14948     Document Type: Review

References (52)

1. Carson DA, Nobori T, Kajander EO, Carrera CJ, Kubota M, Yamanaka H. Methylthioadenosine (MeSAdo) phosphorylase deficiency in malignancy. Adv Exp Med Biol 1988; 250:179-85.
2. Kindler HL, Burris HA, III, Sandler AB, Oliff IA. A phase II multicenter study of L-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer. Invest New Drugs 2009; 27:75-81.
3. Chen ZH, Zhang H, Savarese TM. Gene deletion chemoselectivity: codeletion of the genes for p16(INK4), methylthioadenosine phosphorylase and the alpha and beta-interferons in human pancreatic cell carcinoma cell lines and its implications for chemotherapy. Cancer Res 1996; 56:1083-90.
4. Illei PB, Rusch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res 2003; 9:2108-13. (Pubitemid 36687632)
5. Hustinx SR, Hruban RH, Leoni LM, Iacobuzio- Donahue C, Cameron JL, Yeo CJ, et al. Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in peri-ampullary cancer: a potential new target for chemotherapy. Cancer Biol Ther 2005; 4:83-6. (Pubitemid 41350936)
6. Watanabe F, Takao M, Inoue K, Nishioka J, Nobori T, Shiraishi T, et al. Immunohistochemical diagnosis of methylthioadenosine phosphorylase (MTAP) deficiency in non-small cell lung cancer. Lung Cancer 2009; 63:39-44.
7. García-Castellano JM, Villanueva A, Healey JH, Sowers R, Cordon-Cardo C, Huvos A, et al. Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma. Clin Cancer Res 2002; 8:782-7. (Pubitemid 34742108)
8. Miyazaki S, Nihioka J, Shiraishi T, Matsumine A, Uchida A, Nobori T. Methylthioadenosine phosphorylase deficiency in Japanese osteosarcoma patients. Int J Oncol 2007; 5:1069-76.
9. Chow WA, Bedell V, Gaytan P, Borden E, Goldblum J, Hicks D, et al. Methylthioadenosine phosphorylase gene deletions are frequently detected by fluorescence in situ hybridization in conventional sarcomas. Cancer Genet Cytogenet 2006; 166:95-100.
10. Li W, Su D, Mizobuchi H, Martin DS, Gu B, Gorlick R, et al. Status of methylthioadenosine phosphorylase and its impact on cellular response to L-alanosine and methylmercaptopurine riboside in human soft tissue sarcoma cells. Oncol Res 2004; 14:373-9. (Pubitemid 39070678)
11. Nobori T, Karras JG, Della Ragione F, Waltz TA, Chen PP, et al. Absence of methylthioadenosine phosphorylase in human gliomas. Cancer Res 1991; 51:3193-7.
12. Huang HY, Li SH, Yu SC, Chou FF, Tzeng CC, Hu TH, et al. Homozygous deletion of MTAP gene as a poor prognosticator in gastrointestinal stromal tumors. Clin Cancer Res 2009; 15:6963-72.
13. Wong YF, Chung TK, Cheung TH, Nobori T, Chang AM. MTAP gene deletion in endometrial cancer. Gynecol Obstet Invest 1998; 45:272-6. (Pubitemid 28241185)
14. Powell EL, Leoni LM, Canto MI, Forastiere AA, Iocobuzio-Donahue CA, Wang JS, et al. Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications. Am J Surg Pathol 2005; 29:1497-504. (Pubitemid 41513300)
15. Sommer J, Itani DM, Homlar KC, Forastiere AA, Iocobuzio-Donahue CA, Wang JS, et al. Methylthioadenosine phosphorylase and activated insulin-like growth factor-1 receptor/insulin receptor: potential targets in chordoma. J Pathol 2010; 220:608-17.
16. Karikari CA, Mullendore M, Eshleman JR, Argani P, Leoni LM, Chattopadhyay S, et al. Homozygous deletions of methylthioadenosine phosphorylase in human biliary tract cancers. Mol Cancer Ther 2005; 4:1860-6. (Pubitemid 43056969)
17. Behrmann I, Wallner S, Komyod W, Heinrich PC, Schuierer M, Buettner R, et al. Characterization of methylthioadenosine phosphorylase expression in malignant melanoma. Am J Pathol 2003; 163:683-90. (Pubitemid 36909429)
18. Schmid M, Malicki D, Nobori T, Rosenbach MD, Campbell K, Carson DA, et al. Homozygous deletions of methylthioadenosine phosphorylase (MTAP) are more frequent than p16INK4A (CDKN2) homozygous deletions in primary non-small cell lung cancers (NSCLC). Oncogene 1998; 17:2669-75.
19. Ishii M, Nakazawa K, Wada H, Nishioka J, Nakatani K, Yamada Y, et al. Methylthioadenosine phosphorylase gene is silenced by promoter hypermethylation in human lymphoma cell line DHL-9: another mechanism of enzyme deficiency. Int J Oncol 2005; 26:985-91.
20. Chen ZH, Olopade OI, Savarese TM. Expression of methylthioadenosine phosphorylase cDNA in p16-, MTAP-malignant cells: restoration of methylthioadenosine phosphorylase-dependent salvage pathways and alterations of sensitivity to inhibitors of purine de novo synthesis. Mol Pharmacol 1997; 52:903-11.
21. Tisdale MJ. Methionine synthesis from 5′-methylthioadenosine by tumour cells. Biochem Pharmacol 1983; 32:2915-20. (Pubitemid 13013727)
22. Harasawa H, Yamada Y, Kudoh M, Sugahara K, Soda H, Hirakata Y, et al. Chemotherapy targeting methylthioadenosine phosphorylase (MTAP) deficiency in adult T-cell leukemia (ATL). Leukemia 2002; 16:1799-807.
23. M'Soka TJ, Nishioka J, Taga A, Kato K, Kawasaki H, Yamada Y, et al. Detection of methylthioadenosine phosphorylase (MTAP) and p16 gene deletion in T-cell acute lymphoblastic leukemia by real time quantitative PCR assay. Leukemia 2000; 14:935-40. (Pubitemid 30235074)
24. Traweek ST, Riscoe MK, Ferno AJ, Braziel RM, Magenis RE, Fitchen JH. Methylthioadenosine phosphorylase deficiency in acute leukemia: pathologic, cytogenetic and clinical features. Blood 1988; 71:1568-73.
25. INK4A gene in acute type adult T-cell leukemia. Int J Cancer 1998; 75:51-6.
26. Dreyling MH, Roulston D, Bohlander SK, Vardiman J, Olopade OI. Codeletion of CDKN2 and MTAP genes in a subset of non-Hodgkin's lymphoma may be associated with histologic transformation from low-grade to diffuse large cell lymphoma. Genes Chromosomes Cancer 1998; 22:72-8. (Pubitemid 28217809)
27. Mirebeau D, Acquaviva C, Suciu S, Bertin R, Dastugue N, Robert A, et al. The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951. Haematologica 2006; 91:881-5.
28. Marcé S, Balague O, Colomo L, Martinez A, Holler S, Villamor N, et al. Lack of methylthioadenosine phosphorylase expression in mantle cell lymphoma is associated with shorter survival: implications for a potential targeted therapy. Clin Cancer Res 2006; 12:3754-61. (Pubitemid 44000257)
29. Kadariya Y, Yin B, Tang B, Shinton SA, Quinlivan EP, Hua X, et al. Mice heterozygous for germ-line mutations in methylthioadenosine phosphorylase (MTAP) die prematurely of T-cell lymphoma. Cancer Res 2009; 69:5961-9.
30. Vieira de Oliveira SF, Oliveira MM, Urban CA, de Lima RS, Cavalli IJ, Ribeiro EM. Lack of association between LOH in the 9p region and clinicopathologic parameters in primary breast cancer. Cancer Genet Cytogenet 2010; 200:23-7.
31. Hori H, Tran P, Carrera CJ, Hori Y, Rosenbach MD, Carson DA, et al. Methylthioadenosine phosphorylase cDNA transfection alters sensitivity to depletion of purine and methionine in A549 lung cancer cells. Cancer Res 1996; 56:5653-8. (Pubitemid 26422168)
32. Allegra CJ, Drake JC, Jolivet J, Chabner BA. Inhibition of phosphoribosylaminoimidazolecarboximide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc Natl Acad Sci USA 1985; 82:4881-5. (Pubitemid 15249910)
33. Swann PF, Waters TR, Moulton DC, Xu YZ, Zheng Q, Edwards M, et al. Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine. Science 1996; 273:1109-11.
34. Rubin J, Hineman V, Moertel CG, Schutt AJ, Hahn RG. A phase II clinical trial of L-alanosine in advanced large bowel carcinoma. Am J Clin Oncol 1983; 6:191-3. (Pubitemid 13102157)
35. Creagan ET, Long HJ, Ahmann DL, Green SJ. Phase II evaluation of L-alanosine (NSC-153353) for patients with disseminated malignant melanoma Am J Clin Oncol 1984; 7:543-4.
36. Creagan ET, Schutt AJ, Ingle JN, O'Fallon JR. Phase II clinical trial of L-alanosine in advanced upper aerodigestive cancer. Cancer Treat Rep 1983; 67:1047. (Pubitemid 14208714)
37. Von Hoff DD, Green SJ, Neidhart JA, Fabian C, Budd T, Boyd JF, et al. Phase II study of L-alanosine (NSC 153353) in patients with advanced breast cancer. A Southwest Oncology Group Study. Invest New Drugs 1991; 9:87-8.
38. Chattopadhyay S, Moran RG, Goldman ID. Pemetrexed: biochemical and cellular pharmacology, mechanisms and clinical applications. Mol Cancer Therapy 2007; 6:404-17. (Pubitemid 46332443)
39. Tan CT, Wollner N, Trippett T, Goker E, Tong WP, Kheradpour A, et al. Pharmacologic-guided trial of sequential methotrexate and thioguanine in children with advanced malignancies. J Clin Oncol 1994; 12:1955-62. (Pubitemid 24349400)
40. Subhi AL, Tang B, Balsara BR, Altomare DA, Testa JR, Cooper HS, et al. Loss of methylthioadenosine phosphorylase and elevated ornithine decarboxylase is common in pancreatic cancer. Clin Cancer Res 2004; 10:7290-6. (Pubitemid 39487717)
41. Simile MM, Banni S, Angioni E, Carta G, De Miglio MR, Muroni MR, et al. 5′-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication. J Hepatol 2001; 34:386-94. (Pubitemid 32240817)
42. Wolford RW, Riscoe MK, Johnson L, Ferro AJ, Fitchen JH. Effect of 5'-methylthioadenosine (a naturally occurring nucleoside) on murine hematopoiesis. Exp Hematol 1984; 12:867-71. (Pubitemid 15198925)
43. Stramentinoli G, Gennari F. Adenosine derivatives of anti-inflammatory and analgesic activity, and therapeutic compositions which contain them as their active principle. 1984 US patent 4454122.
44. Moratti E. Pharmaceutical compositions containing 5′-deoxy- 5′-methylthioadenosine S-adenosylmethionine and their salts for reducing seborrhea. 1998 US patent 5753213.
45. Moreno B, Hevia H, Santamaria M, Sepulcre J, Munoz J, Garcia-Trevijano ER, et al. Methylthioadenosine reverses brain autoimmune disease. Ann Neurol 2006; 60:323-34. (Pubitemid 44520235)
46. Andreu-Pérez P, Hernandez-Losa J, Moliné T, Gil R, Grueso J, Pujol A, et al. Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth. BMC Cancer 2010; 10:265.
47. Li TW, Zhang Q, Oh P, Xia M, Chen H, Bemanian S, et al. S-Adenosylmethionine and methylthioadenosine inhibit cellular FLICE inhibitory protein expression and induce apoptosis in colon cancer cells. Mol Pharmacol 2009; 76:192-200.
48. Kamatani N, Nelson-Rees WA, Carson DA. Selective killing of human malignant cell lines deficient in methylthioadenosine phosphorylase, a purine metabolic enzyme. Proc Natl Acad Sci USA 1981; 78:1219-23. (Pubitemid 11102192)
49. Lubin M, Lubin A. Selective killing of tumors deficient in methylthioadenosine phosphorylase: a novel strategy. PLoS ONE 2009; 4:5735.
50. Lubin M, Lubin A. Strategy for selective killing of tumors deficient in methylthioadenosine phosphorylase (MTAP): a progress report. Proc Am Assoc Cancer Res 2009; 4:e5735.
51. Clarke DA, Hamilton LD, Philips FS, Sternberg SS. Effects of thioguanine in mammals. Cancer 1956; 9:1092-101.
52. Bertino JR, Johnson-Farley N, Perez RP, Lubin A, Lubin M. Regression of a human T-cell leukemia lacking the methylthioadenosine phosphorylase (MTAP) gene without toxicity of 6-thioguanine (6TG) by pre-treatment with methylthioadenosine. Proc Am Assoc Cancer Res 2010; 5393.