Specific inhibition of p110α subunit of PI3K: Putative therapeutic strategy for KRAS mutant colorectal cancers

Oncotarget

Volumn 7, Issue 42, 2016, Pages 68546-68558

  Fernandes, Maria Sofia ^a,b   Melo, Soraia ^a,b,c   Velho, Sérgia ^a,b   Carneiro, Patrícia ^a,b   Carneiro, Fátima ^a,b,c,d   Seruca, Raquel ^a,b,c  

^a UNIVERSITY OF PORTO   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

^c University of Porto   (Portugal)

^d Universidade do Porto   (Portugal)

Author keywords

BYL719; Colorectal cancer; KRAS; PI3K p110 ; Targeted therapies

Indexed keywords

ALPELISIB; CYCLIN D1; K RAS PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE P110 ALPHA; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE; PROTEIN BAD; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; X LINKED INHIBITOR OF APOPTOSIS; KRAS PROTEIN, HUMAN; NVP-BYL719; PIK3CA PROTEIN, HUMAN; PROTEIN P21; THIAZOLE DERIVATIVE;

APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL MUTANT; CELL VIABILITY; COLORECTAL CANCER; COLORECTAL CANCER CELL LINE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; DRUG MECHANISM; ENZYME INHIBITION; GENE FUNCTION; GENE MUTATION; GENE SILENCING; HCT 116 CELL LINE; HUMAN; HUMAN CELL; IN VITRO STUDY; ONCOGENE K RAS; PIK3CA GENE; PROTEIN EXPRESSION; PROTEIN TARGETING; SW480 CELL LINE; ANTAGONISTS AND INHIBITORS; CELL CYCLE; CELL SURVIVAL; COLORECTAL TUMOR; DRUG EFFECTS; GENETICS; METABOLISM; MUTATION; PATHOLOGY; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TUMOR CELL LINE; WESTERN BLOTTING;

APOPTOSIS; BLOTTING, WESTERN; CELL CYCLE; CELL LINE, TUMOR; CELL SURVIVAL; CLASS I PHOSPHATIDYLINOSITOL 3-KINASES; COLORECTAL NEOPLASMS; HCT116 CELLS; HUMANS; MUTATION; PROTO-ONCOGENE PROTEINS P21(RAS); RNA INTERFERENCE; SIGNAL TRANSDUCTION; THIAZOLES;

EID: 85014747304     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: None     Document Type: Article

References (53)

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65:87-108.
2. Markowitz SD and Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. The New England journal of medicine. 2009; 361:2449-2460.
3. Lievre A, Blons H and Laurent-Puig P. Oncogenic mutations as predictive factors in colorectal cancer. Oncogene. 2010; 29:3033-3043.
4. De Roock W, De Vriendt V, Normanno N, Ciardiello F and Tejpar S. KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. The Lancet Oncology. 2011; 12:594-603.
5. Velho S, Corso G, Oliveira C and Seruca R. KRAS signaling pathway alterations in microsatellite unstable gastrointestinal cancers. Advances in cancer research. 2010; 109:123-143.
6. Oliveira C, Velho S, Moutinho C, Ferreira A, Preto A, Domingo E, Capelinha AF, Duval A, Hamelin R, Machado JC, Schwartz S, Jr., Carneiro F and Seruca R. KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression. Oncogene. 2007; 26:158-163.
7. Oliveira C, Westra JL, Arango D, Ollikainen M, Domingo E, Ferreira A, Velho S, Niessen R, Lagerstedt K, Alhopuro P, Laiho P, Veiga I, Teixeira MR, Ligtenberg M, Kleibeuker JH, Sijmons RH, et al. Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status. Human molecular genetics. 2004; 13:2303-2311.
8. Velho S, Moutinho C, Cirnes L, Albuquerque C, Hamelin R, Schmitt F, Carneiro F, Oliveira C and Seruca R. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: primary or secondary genetic events in colorectal carcinogenesis BMC cancer. 2008; 8:255.
9. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B and Velculescu VE. Tumorigenesis: RAF/ RAS oncogenes and mismatch-repair status. Nature. 2002; 418:934.
10. Velho S, Oliveira C, Ferreira A, Ferreira AC, Suriano G, Schwartz S, Jr., Duval A, Carneiro F, Machado JC, Hamelin R and Seruca R. The prevalence of PIK3CA mutations in gastric and colon cancer. European journal of cancer. 2005; 41:1649-1654.
11. Weng W, Feng J, Qin H and Ma Y. Molecular therapy of colorectal cancer: progress and future directions. International journal of cancer. 2015; 136:493-502.
12. Welch S, Spithoff K, Rumble RB, Maroun J and Gastrointestinal Cancer Disease Site G. Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review. Annals of oncology. 2010; 21:1152-1162.
13. Ciardiello F and Tortora G. EGFR antagonists in cancer treatment. The New England journal of medicine. 2008; 358:1160-1174.
14. Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF and Schilsky RL. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. Journal of clinical oncology. 2009; 27:2091-2096.
15. Allegra CJ, Rumble RB, Hamilton SR, Mangu PB, Roach N, Hantel A and Schilsky RL. Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015. Journal of clinical oncology. 2016; 34:179-185.
16. Irahara N, Baba Y, Nosho K, Shima K, Yan L, Dias- Santagata D, Iafrate AJ, Fuchs CS, Haigis KM and Ogino S. NRAS mutations are rare in colorectal cancer. Diagnostic molecular pathology. 2010; 19:157-163.
17. Pylayeva-Gupta Y, Grabocka E and Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nature reviews Cancer. 2011; 11:761-774.
18. Sebolt-Leopold JS and Herrera R. Targeting the mitogenactivated protein kinase cascade to treat cancer. Nature reviews Cancer. 2004; 4:937-947.
19. Fernandes MS, Carneiro F, Oliveira C and Seruca R. Colorectal cancer and RASSF family--a special emphasis on RASSF1A. International journal of cancer. 2013; 132:251-258.
20. Liu P, Cheng H, Roberts TM and Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nature reviews Drug discovery. 2009; 8:627-644.
21. Vanhaesebroeck B, Stephens L and Hawkins P. PI3K signalling: the path to discovery and understanding. Nature reviews Molecular cell biology. 2012; 13:195-203.
22. Manning BD and Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007; 129:1261-1274.
23. Semba S, Itoh N, Ito M, Harada M and Yamakawa M. The in vitro and in vivo effects of 2-(4-morpholinyl)- 8-phenyl-chromone (LY294002), a specific inhibitor of phosphatidylinositol 3'-kinase, in human colon cancer cells. Clinical cancer research. 2002; 8:1957-1963.
24. Thorpe LM, Yuzugullu H and Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nature reviews Cancer. 2015; 15:7-24.
25. Furet P, Guagnano V, Fairhurst RA, Imbach-Weese P, Bruce I, Knapp M, Fritsch C, Blasco F, Blanz J, Aichholz R, Hamon J, Fabbro D and Caravatti G. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorganic & medicinal chemistry letters. 2013; 23:3741-3748.
26. Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, Kauffmann A, Guthy D, Erdmann D, De Pover A, Furet P, Gao H, Ferretti S, Wang Y, Trappe J, Brachmann SM, et al. Characterization of the novel and specific PI3Kalpha inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Molecular cancer therapeutics. 2014; 13:1117-1129.
27. Samatar AA and Poulikakos PI. Targeting RAS-ERK signalling in cancer: promises and challenges. Nature reviews Drug discovery. 2014; 13:928-942.
28. Rodon J, Dienstmann R, Serra V and Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nature reviews Clinical oncology. 2013; 10:143-153.
29. Castellano E and Downward J. RAS Interaction with PI3K: More Than Just Another Effector Pathway. Genes Cancer. 2011; 2:261-74. doi: 10.1177/1947601911408079.
30. Di Nicolantonio F, Arena S, Tabernero J, Grosso S, Molinari F, Macarulla T, Russo M, Cancelliere C, Zecchin D, Mazzucchelli L, Sasazuki T, Shirasawa S, Geuna M, Frattini M, Baselga J, Gallicchio M, et al. Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus. The Journal of clinical investigation. 2010; 120:2858-2866.
31. Kim A, Lee JE, Lee SS, Kim C, Lee SJ, Jang WS and Park S. Coexistent mutations of KRAS and PIK3CA affect the efficacy of NVP-BEZ235, a dual PI3K/MTOR inhibitor, in regulating the PI3K/MTOR pathway in colorectal cancer. International journal of cancer. 2013; 133:984-996.
32. Janku F, Tsimberidou AM, Garrido-Laguna I, Wang X, Luthra R, Hong DS, Naing A, Falchook GS, Moroney JW, Piha-Paul SA, Wheler JJ, Moulder SL, Fu S and Kurzrock R. PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors. Molecular cancer therapeutics. 2011; 10:558-565.
33. Janku F, Wheler JJ, Naing A, Falchook GS, Hong DS, Stepanek VM, Fu S, Piha-Paul SA, Lee JJ, Luthra R, Tsimberidou AM and Kurzrock R. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer research. 2013; 73:276-284.
34. Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M and Baselga J. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. Journal of clinical oncology. 2012; 30:282-290.
35. Ihle NT, Lemos R, Jr., Wipf P, Yacoub A, Mitchell C, Siwak D, Mills GB, Dent P, Kirkpatrick DL and Powis G. Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance. Cancer research. 2009; 69:143-150.
36. Murillo MM, Zelenay S, Nye E, Castellano E, Lassailly F, Stamp G and Downward J. RAS interaction with PI3K p110alpha is required for tumor-induced angiogenesis. The Journal of clinical investigation. 2014; 124:3601-3611.
37. Gupta S, Ramjaun AR, Haiko P, Wang Y, Warne PH, Nicke B, Nye E, Stamp G, Alitalo K and Downward J. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell. 2007; 129:957-968.
38. Danial NN. BAD: undertaker by night, candyman by day. Oncogene. 2008; 27:S53-70.
39. Eckelman BP, Salvesen GS and Scott FL. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO reports. 2006; 7:988-994.
40. Alao JP. The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Molecular cancer. 2007; 6:24.
41. Stacey DW. Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells. Current opinion in cell biology. 2003; 15:158-163.
42. Yang K, Hitomi M and Stacey DW. Variations in cyclin D1 levels through the cell cycle determine the proliferative fate of a cell. Cell division. 2006; 1:32.
43. Pyo CW, Choi JH, Oh SM and Choi SY. Oxidative stress-induced cyclin D1 depletion and its role in cell cycle processing. Biochimica et biophysica acta. 2013; 1830:5316-5325.
44. Sartore-Bianchi A, Loupakis F, Argiles G and Prager GW. Challenging chemoresistant metastatic colorectal cancer: therapeutic strategies from the clinic and from the laboratory. Annals of oncology. 2016.
45. Gobin B, Huin MB, Lamoureux F, Ory B, Charrier C, Lanel R, Battaglia S, Redini F, Lezot F, Blanchard F and Heymann D. BYL719, a new alpha-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma. International journal of cancer. 2015; 136:784-796.
46. Wong CH, Ma BB, Cheong HT, Hui CW, Hui EP and Chan AT. Preclinical evaluation of PI3K inhibitor BYL719 as a single agent and its synergism in combination with cisplatin or MEK inhibitor in nasopharyngeal carcinoma (NPC). American journal of cancer research. 2015; 5:1496-1506.
47. Keam B, Kim S, Ahn YO, Kim TM, Lee SH, Kim DW and Heo DS. In vitro anticancer activity of PI3K alpha selective inhibitor BYL719 in head and neck cancer. Anticancer research. 2015; 35:175-182.
48. De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, Van Cutsem E, O'Callaghan CJ, Khambata-Ford S, Zalcberg JR, Simes J, Karapetis CS, et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. Jama. 2010; 304:1812-1820.
49. Bieging KT, Mello SS and Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nature reviews Cancer. 2014; 14:359-370.
50. Medico E, Russo M, Picco G, Cancelliere C, Valtorta E, Corti G, Buscarino M, Isella C, Lamba S, Martinoglio B, Veronese S, Siena S, Sartore-Bianchi A, Beccuti M, Mottolese M, Linnebacher M, et al. The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets. Nature communications. 2015; 6:7002.
51. Ahmed D, Eide PW, Eilertsen IA, Danielsen SA, Eknaes M, Hektoen M, Lind GE and Lothe RA. Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis. 2013; 2:e71.
52. Leroy C, Ramos P, Cornille K, Bonenfant D, Fritsch C, Voshol H and Bentires-Alj M. Activation of IGF1R/ p110beta/AKT/mTOR confers resistance to alpha-specific PI3K inhibition. Breast cancer research. 2016; 18:41.
53. Belharazem D, Magdeburg J, Berton AK, Beissbarth L, Sauer C, Sticht C, Marx A, Hofheinz R, Post S, Kienle P and Strobel P. Carcinoma of the colon and rectum with deregulation of insulin-like growth factor 2 signaling: clinical and molecular implications. Journal of gastroenterology. 2016.