Dual Phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor is an effective radiosensitizer for colorectal cancer

Cancer Letters

Volumn 357, Issue 2, 2015, Pages 582-590

  Chen, Yu Hsuan ^a,b   Wei, Ming Feng ^b   Wang, Chun Wei ^a,b   Lee, Hsiao Wei ^a,b   Pan, Shiow Lin ^b   Gao, Ming ^a,b   Kuo, Sung Hsin ^a,b,c   Cheng, Ann Lii ^a,b,c   Teng, Che Ming ^b  

^a NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^c NATIONAL TAIWAN UNIVERSITY   (Taiwan)

Author keywords

BEZ235; Colorectal cancer; PI3K Akt mTOR; Radiation

Indexed keywords

ATM PROTEIN; DACTOLISIB; DNA DEPENDENT PROTEIN KINASE; INITIATION FACTOR 4E; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN KINASE B; PROTEIN S6; AKTIP PROTEIN, HUMAN; APOPTOSIS REGULATORY PROTEIN; IMIDAZOLE DERIVATIVE; MTOR PROTEIN, HUMAN; PHOSPHATIDYLINOSITOL 3 KINASE; QUINOLINE DERIVATIVE; RADIOSENSITIZING AGENT; SIGNAL TRANSDUCING ADAPTOR PROTEIN; TARGET OF RAPAMYCIN KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CELL CYCLE G1 PHASE; CELL CYCLE PROGRESSION; CELL SURVIVAL; CELL VIABILITY; COLORECTAL CANCER; COLORECTAL CANCER CELL LINE; CONTROLLED STUDY; DNA REPAIR; DOUBLE STRANDED DNA BREAK; ENZYME ACTIVATION; FEMALE; G1 PHASE CELL CYCLE CHECKPOINT; HCT116 CELL LINE; HT 29 CELL LINE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; IRRADIATION; MOUSE; NONHUMAN; PHARMACOLOGICAL BLOCKING; PROTEIN EXPRESSION; RADIOSENSITIVITY; RADIOSENSITIZATION; SIGNAL TRANSDUCTION; SW620 CELL LINE; TUMOR VOLUME; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMORADIOTHERAPY; COLORECTAL NEOPLASMS; CONFOCAL MICROSCOPY; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; IMMUNOHISTOCHEMISTRY; METABOLISM; PATHOLOGY; RADIATION DOSE; RADIATION RESPONSE; SCID MOUSE; TUMOR CELL LINE; WESTERN BLOTTING;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; APOPTOSIS REGULATORY PROTEINS; BLOTTING, WESTERN; CELL LINE, TUMOR; CELL SURVIVAL; CHEMORADIOTHERAPY; COLORECTAL NEOPLASMS; DNA BREAKS, DOUBLE-STRANDED; DOSE-RESPONSE RELATIONSHIP, DRUG; DOSE-RESPONSE RELATIONSHIP, RADIATION; FEMALE; G1 PHASE; HCT116 CELLS; HUMANS; IMIDAZOLES; IMMUNOHISTOCHEMISTRY; MICE, SCID; MICROSCOPY, CONFOCAL; PHOSPHATIDYLINOSITOL 3-KINASES; QUINOLINES; RADIATION TOLERANCE; RADIATION-SENSITIZING AGENTS; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84920858254     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2014.12.015     Document Type: Article

References (37)

1. Glynne-Jones R., Harrison M. Locally advanced rectal cancer: what is the evidence for induction chemoradiation?. Oncologist 2007, 12(11):1309-1318.
2. Swedish Rectal Cancer Trial Improved survival with preoperative radiotherapy in resectable rectal cancer. N. Engl. J. Med 1997, 336(21):980-987.
3. Kapiteijn E., Marijnen C.A., Nagtegaal I.D., Putter H., Steup W.H., Wiggers T., et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N. Engl. J. Med 2001, 345(9):638-646.
4. Sauer R., Becker H., Hohenberger W., Rodel C., Wittekind C., Fietkau R., et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N. Engl. J. Med 2004, 351(17):1731-1740.
5. Maas M., Nelemans P.J., Valentini V., Das P., Rodel C., Kuo L.J., et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010, 11(9):835-844.
6. Crane C.H., Eng C., Feig B.W., Das P., Skibber J.M., Chang G.J., et al. Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer. Int. J. Radiat. Oncol. Biol. Phys 2010, 76(3):824-830.
7. Wolpin B.M., Meyerhardt J.A., Mamon H.J., Mayer R.J. Adjuvant treatment of colorectal cancer. C.A, Cancer. J. Clin 2007, 57(3):168-185.
8. Sanghera P., Wong D.W., McConkey C.C., Geh J.I., Hartley A. Chemoradiotherapy for rectal cancer: an updated analysis of factors affecting pathological response. Clin. Oncol. (R. Coll. Radiol.) 2008, 20:176-183.
9. Willett C.G., Duda D.G., di Tomaso E., Boucher Y., Ancukiewicz M., Sahani D.V., et al. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J. Clin. Oncol 2009, 27(2):3020-3026.
10. Johnson S.M., Gulhati P., Rampy B.A., Han Y., Rychahou P.G., Doan H.Q., et al. Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer. J. Am. Coll. Surg 2010, 210(5):767-776. 776-768.
11. Zhang Y.J., Dai Q., Sun D.F., Xiong H., Tian X.Q., Gao F.H., et al. mTOR signaling pathway is a target for the treatment of colorectal cancer. Ann. Surg. Oncol 2009, 16(9):2617-2628.
12. Kobayashi M., Nagata S., Iwasaki T., Yanagihara K., Saitoh I., Karouji Y., et al. Dedifferentiation of adenocarcinomas by activation of phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. U.S.A. 1999, 96(9):4874-4879.
13. Philp A.J., Campbell I.G., Leet C., Vincan E., Rockman S.P., Whitehead R.H., et al. The phosphatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Res 2001, 61(20):7426-7429.
14. Roy H.K., Olusola B.F., Clemens D.L., Karolski W.J., Ratashak A., Lynch H.T., et al. AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis. Carcinogenesis 2002, 23(1):201-205.
15. Shaw R.J., Cantley L.C. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006, 441(7092):424-430.
16. Kinkade C.W., Castillo-Martin M., Puzio-Kuter A., Yan J., Foster T.H., Gao H., et al. Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model. J. Clin. Invest 2008, 118(9):3051-3064.
17. Rodriguez-Viciana P., Warne P.H., Dhand R., Vanhaesebroeck B., Gout I., Fry M.J., et al. Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature 1994, 370(6490):527-532.
18. Gupta S., Ramjaun A.R., Haiko P., Wang Y., Warne P.H., Nicke B., et al. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell 2007, 129(5):957-968.
19. Andreyev H.J., Norman A.R., Cunningham D., Oates J., Dix B.R., Iacopetta B.J., et al. Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br. J. Cancer 2001, 85(5):692-696.
20. Normanno N., Tejpar S., Morgillo F., De Luca A., Van Cutsem E., Ciardiello F. Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat. Rev. Clin. Oncol 2009, 6(9):519-527.
21. Sunavala-Dossabhoy G., Fowler M., De Benedetti A. Translation of the radioresistance kinase TLK1B is induced by gamma-irradiation through activation of mTOR and phosphorylation of 4E-BP1. BMC Mol. Biol 2004, 5:1.
22. Konstantinidou G., Bey E.A., Rabellino A., Schuster K., Maira M.S., Gazdar A.F., et al. Dual phosphoinositide 3-kinase/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutations. Cancer Res 2009, 69(19):7644-7652.
23. Gil del Alcazar C.R., Hardebeck M.C., Mukherjee B., Tomimatasu N., Gao X., Yan J., et al. Inhibition of DNA double-strand break repair by the dual PI3K/mTOR inhibitor NVP-BEZ235 as a strategy for radiosensitization of glioblastoma. Clin. Cancer Res 2014, 20(5):1235-1248.
24. Kucherlapati M.H., Esfahani S., Habibollahi P., Wang J., Still E.R., Bronson R.T., et al. Genotype directed therapy in murine mismatch repair deficient tumors. PLoS ONE 2013, 8(7):e68817.
25. Khanna K.K., Jackson S.P. DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet 2001, 27(3):247-254.
26. Burma S., Chen D.J. Role of DNA-PK in the cellular response to DNA double-strand breaks. DNA Repair (Amst) 2004, 3(8-9):909-918.
27. Lavin M.F. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat. Rev. Mol. Cell Biol 2008, 9(10):759-769.
28. Mukherjee B., Tomimatsu N., Amancherla K., Camacho C.V., Pichamoorthy N., Burma S. The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses. Neoplasia 2012, 14(1):34-43.
29. Kuo S.H., Hsu C.H., Chen L.T., Lu Y.S., Lin C.H., Yeh P.Y., et al. Lack of compensatory pAKT activation and eIF4E phosphorylation of lymphoma cells towards mTOR inhibitor, RAD001. Eur. J. Cancer 2011, 47(8):1244-1257.
30. Kuo S.H., Chen L.T., Lin C.W., Wu M.S., Hsu P.N., Tsai H.J., et al. Detection of the Helicobacter pylori CagA protein in gastric mucosa-associated lymphoid tissue lymphoma cells: clinical and biological significance. Blood, Cancer J. 2013, 3:e125.
31. Li H.F., Kim J.S., Waldman T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat. Oncol 2009, 4:43.
32. Xia S., Zhao Y., Yu S., Zhang M. Activated PI3K/Akt/COX-2 pathway induces resistance to radiation in human cervical cancer HeLa cells. Cancer Biother. Radiopharm 2010, 25(3):317-323.
33. Bjornsti M.A., Houghton P.J. The TOR pathway: a target for cancer therapy. Nat. Rev. Cancer 2004, 4(5):335-348.
34. Nicholson K.M., Anderson N.G. The protein kinase B/Akt signalling pathway in human malignancy. Cell. Signal 2002, 14(5):381-395.
35. Kuger S., Graus D., Brendtke R., Gunther N., Katzer A., Lutyj P., et al. Radiosensitization of glioblastoma cell lines by the dual PI3K and mTOR inhibitor NVP-BEZ235 depends on drug-irradiation schedule. Transl. Oncol 2013, 6(2):169-179.
36. Fokas E., Yoshimura M., Prevo R., Higgins G., Hackl W., Maira S.M., et al. NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity. Radiat. Oncol 2012, 7:48.
37. Peyton J.D., Rodon Ahnert J., Burris H., Britten C., Chen L.C., Tabernero J., et al. A dose-escalation study with the novel formulation of the oral pan-class I PI3K inhibitor BEZ235, solid dispersion system (SDS) sachet, in patients with advanced solid tumors. J. Clin. Oncol 2011, 29:3066. ASCO Annual Meeting Proceedings, Abstract.