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Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells.

Benjamin D, Robay D, Hindupur SK, Pohlmann J, Colombi M, El-Shemerly MY, Maira SM, Moroni C, Lane HA, Hall MN.

Cell Rep. 2018 Dec 11;25(11):3047-3058.e4. doi: 10.1016/j.celrep.2018.11.043.


Increasing metabolic stability via the deuterium kinetic isotope effect: An example from a proline-amide-urea aminothiazole series of phosphatidylinositol-3 kinase alpha inhibitors.

Fairhurst RA, Caravatti G, Guagnano V, Aichholz R, Blanz J, Blasco F, Wipfli P, Fritsch C, Maira SM, Schnell C, Seiler FH.

Bioorg Med Chem Lett. 2016 Oct 1;26(19):4729-4734. doi: 10.1016/j.bmcl.2016.08.041. Epub 2016 Aug 17.


Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition.

Herkert B, Kauffmann A, Mollé S, Schnell C, Ferrat T, Voshol H, Juengert J, Erasimus H, Marszalek G, Kazic-Legueux M, Billy E, Ruddy D, Stump M, Guthy D, Ristov M, Calkins K, Maira SM, Sellers WR, Hofmann F, Hall MN, Brachmann SM.

Cancer Res. 2016 Jan 15;76(2):390-402. doi: 10.1158/0008-5472.CAN-14-3358. Epub 2015 Nov 17.


Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials.

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, Maira SM, Wilson C, Boehm M, Garcia-Echeverria C, Chene P, Wiesmann M, Cozens R, Lehar J, Schlegel R, Caravatti G, Hofmann F, Sellers WR.

Mol Cancer Ther. 2014 May;13(5):1117-29. doi: 10.1158/1535-7163.MCT-13-0865. Epub 2014 Mar 7.


Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110α.

Gritsman K, Yuzugullu H, Von T, Yan H, Clayton L, Fritsch C, Maira SM, Hollingworth G, Choi C, Khandan T, Paktinat M, Okabe RO, Roberts TM, Zhao JJ.

J Clin Invest. 2014 Apr;124(4):1794-809. doi: 10.1172/JCI69927. Epub 2014 Feb 24.


A genetic mouse model of invasive endometrial cancer driven by concurrent loss of Pten and Lkb1 Is highly responsive to mTOR inhibition.

Cheng H, Liu P, Zhang F, Xu E, Symonds L, Ohlson CE, Bronson RT, Maira SM, Di Tomaso E, Li J, Myers AP, Cantley LC, Mills GB, Zhao JJ.

Cancer Res. 2014 Jan 1;74(1):15-23. doi: 10.1158/0008-5472.CAN-13-0544. Epub 2013 Dec 9.


Spatially distinct roles of class Ia PI3K isoforms in the development and maintenance of PTEN hamartoma tumor syndrome.

Wang Q, Von T, Bronson R, Ruan M, Mu W, Huang A, Maira SM, Zhao JJ.

Genes Dev. 2013 Jul 15;27(14):1568-80. doi: 10.1101/gad.216069.113.


Radiosensitization of prostate cancer cells by the dual PI3K/mTOR inhibitor BEZ235 under normoxic and hypoxic conditions.

Potiron VA, Abderrahmani R, Giang E, Chiavassa S, Di Tomaso E, Maira SM, Paris F, Supiot S.

Radiother Oncol. 2013 Jan;106(1):138-46. doi: 10.1016/j.radonc.2012.11.014. Epub 2013 Jan 12. Erratum in: Radiother Oncol. 2013 May;107(2):263. Abderrhamani, Rym [corrected to Abderrahmani, Rym].


Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention.

Jia S, Gao X, Lee SH, Maira SM, Wu X, Stack EC, Signoretti S, Loda M, Zhao JJ, Roberts TM.

Cancer Discov. 2013 Jan;3(1):44-51. doi: 10.1158/2159-8290.CD-12-0262. Epub 2012 Dec 20.


K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo.

Hofmann I, Weiss A, Elain G, Schwaederle M, Sterker D, Romanet V, Schmelzle T, Lai A, Brachmann SM, Bentires-Alj M, Roberts TM, Sellers WR, Hofmann F, Maira SM.

PLoS One. 2012;7(8):e44146. doi: 10.1371/journal.pone.0044146. Epub 2012 Aug 31.


Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations.

Brachmann SM, Kleylein-Sohn J, Gaulis S, Kauffmann A, Blommers MJ, Kazic-Legueux M, Laborde L, Hattenberger M, Stauffer F, Vaxelaire J, Romanet V, Henry C, Murakami M, Guthy DA, Sterker D, Bergling S, Wilson C, Brümmendorf T, Fritsch C, Garcia-Echeverria C, Sellers WR, Hofmann F, Maira SM.

Mol Cancer Ther. 2012 Aug;11(8):1747-57. doi: 10.1158/1535-7163.MCT-11-1021. Epub 2012 May 31.


mTOR inhibitors synergize on regression, reversal of gene expression, and autophagy in hepatocellular carcinoma.

Thomas HE, Mercer CA, Carnevalli LS, Park J, Andersen JB, Conner EA, Tanaka K, Matsutani T, Iwanami A, Aronow BJ, Manway L, Maira SM, Thorgeirsson SS, Mischel PS, Thomas G, Kozma SC.

Sci Transl Med. 2012 Jun 20;4(139):139ra84. doi: 10.1126/scitranslmed.3003923. Epub 2012 Apr 25.


NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity.

Fokas E, Yoshimura M, Prevo R, Higgins G, Hackl W, Maira SM, Bernhard EJ, McKenna WG, Muschel RJ.

Radiat Oncol. 2012 Mar 27;7:48. doi: 10.1186/1748-717X-7-48.


Multi-level targeting of the phosphatidylinositol-3-kinase pathway in non-small cell lung cancer cells.

Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH.

PLoS One. 2012;7(2):e31331. doi: 10.1371/journal.pone.0031331. Epub 2012 Feb 15.


Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor.

Maira SM, Pecchi S, Huang A, Burger M, Knapp M, Sterker D, Schnell C, Guthy D, Nagel T, Wiesmann M, Brachmann S, Fritsch C, Dorsch M, Chène P, Shoemaker K, De Pover A, Menezes D, Martiny-Baron G, Fabbro D, Wilson CJ, Schlegel R, Hofmann F, García-Echeverría C, Sellers WR, Voliva CF.

Mol Cancer Ther. 2012 Feb;11(2):317-28. doi: 10.1158/1535-7163.MCT-11-0474. Epub 2011 Dec 21.


Dual inhibition of the PI3K/mTOR pathway increases tumor radiosensitivity by normalizing tumor vasculature.

Fokas E, Im JH, Hill S, Yameen S, Stratford M, Beech J, Hackl W, Maira SM, Bernhard EJ, McKenna WG, Muschel RJ.

Cancer Res. 2012 Jan 1;72(1):239-48. doi: 10.1158/0008-5472.CAN-11-2263. Epub 2011 Nov 22.


PI3K inhibitors for cancer treatment: five years of preclinical and clinical research after BEZ235.

Maira SM.

Mol Cancer Ther. 2011 Nov;10(11):2016. doi: 10.1158/1535-7163.MCT-11-0792. No abstract available.


Antitumor activity of NVP-BKM120--a selective pan class I PI3 kinase inhibitor showed differential forms of cell death based on p53 status of glioma cells.

Koul D, Fu J, Shen R, LaFortune TA, Wang S, Tiao N, Kim YW, Liu JL, Ramnarian D, Yuan Y, Garcia-Echevrria C, Maira SM, Yung WK.

Clin Cancer Res. 2012 Jan 1;18(1):184-95. doi: 10.1158/1078-0432.CCR-11-1558. Epub 2011 Nov 7.


ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer.

Miller TW, Balko JM, Fox EM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, Jiang A, Smith RA, Maira SM, Manning HC, González-Angulo AM, Mills GB, Higham C, Chanthaphaychith S, Kuba MG, Miller WR, Shyr Y, Arteaga CL.

Cancer Discov. 2011 Sep;1(4):338-51. doi: 10.1158/2159-8290.CD-11-0101. Epub 2011 Jul 20.


Reduced pathological angiogenesis and tumor growth in mice lacking GPR4, a proton sensing receptor.

Wyder L, Suply T, Ricoux B, Billy E, Schnell C, Baumgarten BU, Maira SM, Koelbing C, Ferretti M, Kinzel B, Müller M, Seuwen K, Ludwig MG.

Angiogenesis. 2011 Dec;14(4):533-44. doi: 10.1007/s10456-011-9238-9. Epub 2011 Nov 2.


Inhibition of DNA-dependent protein kinase induces accelerated senescence in irradiated human cancer cells.

Azad A, Jackson S, Cullinane C, Natoli A, Neilsen PM, Callen DF, Maira SM, Hackl W, McArthur GA, Solomon B.

Mol Cancer Res. 2011 Dec;9(12):1696-707. doi: 10.1158/1541-7786.MCR-11-0312. Epub 2011 Oct 18.


Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer.

Burger MT, Pecchi S, Wagman A, Ni ZJ, Knapp M, Hendrickson T, Atallah G, Pfister K, Zhang Y, Bartulis S, Frazier K, Ng S, Smith A, Verhagen J, Haznedar J, Huh K, Iwanowicz E, Xin X, Menezes D, Merritt H, Lee I, Wiesmann M, Kaufman S, Crawford K, Chin M, Bussiere D, Shoemaker K, Zaror I, Maira SM, Voliva CF.

ACS Med Chem Lett. 2011 Aug 26;2(10):774-9. doi: 10.1021/ml200156t. eCollection 2011 Oct 13.


Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia.

Chapuis N, Tamburini J, Green AS, Vignon C, Bardet V, Neyret A, Pannetier M, Willems L, Park S, Macone A, Maira SM, Ifrah N, Dreyfus F, Herault O, Lacombe C, Mayeux P, Bouscary D.

Clin Cancer Res. 2010 Nov 15;16(22):5424-35. doi: 10.1158/1078-0432.CCR-10-1102. Epub 2010 Sep 30.


Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma.

Buonamici S, Williams J, Morrissey M, Wang A, Guo R, Vattay A, Hsiao K, Yuan J, Green J, Ospina B, Yu Q, Ostrom L, Fordjour P, Anderson DL, Monahan JE, Kelleher JF, Peukert S, Pan S, Wu X, Maira SM, García-Echeverría C, Briggs KJ, Watkins DN, Yao YM, Lengauer C, Warmuth M, Sellers WR, Dorsch M.

Sci Transl Med. 2010 Sep 29;2(51):51ra70. doi: 10.1126/scitranslmed.3001599.


From the bench to the bed side: PI3K pathway inhibitors in clinical development.

Maira SM, Finan P, Garcia-Echeverria C.

Curr Top Microbiol Immunol. 2010;347:209-39. doi: 10.1007/82_2010_60. Review.


Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors.

Carretero J, Shimamura T, Rikova K, Jackson AL, Wilkerson MD, Borgman CL, Buttarazzi MS, Sanofsky BA, McNamara KL, Brandstetter KA, Walton ZE, Gu TL, Silva JC, Crosby K, Shapiro GI, Maira SM, Ji H, Castrillon DH, Kim CF, García-Echeverría C, Bardeesy N, Sharpless NE, Hayes ND, Kim WY, Engelman JA, Wong KK.

Cancer Cell. 2010 Jun 15;17(6):547-59. doi: 10.1016/j.ccr.2010.04.026.


NVP-BEZ235 as a new therapeutic option for sarcomas.

Manara MC, Nicoletti G, Zambelli D, Ventura S, Guerzoni C, Landuzzi L, Lollini PL, Maira SM, García-Echeverría C, Mercuri M, Picci P, Scotlandi K.

Clin Cancer Res. 2010 Jan 15;16(2):530-40. doi: 10.1158/1078-0432.CCR-09-0816. Epub 2010 Jan 12.


High metastatic efficiency of human sarcoma cells in Rag2/gammac double knockout mice provides a powerful test system for antimetastatic targeted therapy.

Nanni P, Nicoletti G, Landuzzi L, Croci S, Murgo A, Palladini A, Antognoli A, Ianzano ML, Stivani V, Grosso V, Maira SM, García-Echeverría C, Scotlandi K, De Giovanni C, Lollini PL.

Eur J Cancer. 2010 Feb;46(3):659-68. doi: 10.1016/j.ejca.2009.11.018. Epub 2009 Dec 22.


Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells.

Brachmann SM, Hofmann I, Schnell C, Fritsch C, Wee S, Lane H, Wang S, Garcia-Echeverria C, Maira SM.

Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22299-304. doi: 10.1073/pnas.0905152106. Epub 2009 Dec 10.


Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition.

Faber AC, Li D, Song Y, Liang MC, Yeap BY, Bronson RT, Lifshits E, Chen Z, Maira SM, García-Echeverría C, Wong KK, Engelman JA.

Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19503-8. doi: 10.1073/pnas.0905056106. Epub 2009 Oct 22.


NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas.

Liu TJ, Koul D, LaFortune T, Tiao N, Shen RJ, Maira SM, Garcia-Echevrria C, Yung WK.

Mol Cancer Ther. 2009 Aug;8(8):2204-10. doi: 10.1158/1535-7163.MCT-09-0160. Epub 2009 Aug 11.


Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein.

Piao L, Li Y, Yang KJ, Park KA, Byun HS, Won M, Hong J, Kim JL, Kweon GR, Hur GM, Seok JH, Cho JY, Chun T, Hess D, Sack R, Maira SM, Brazil DP, Hemmings BA, Park J.

BMC Cell Biol. 2009 Jul 15;10:53. doi: 10.1186/1471-2121-10-53.


Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235.

McMillin DW, Ooi M, Delmore J, Negri J, Hayden P, Mitsiades N, Jakubikova J, Maira SM, Garcia-Echeverria C, Schlossman R, Munshi NC, Richardson PG, Anderson KC, Mitsiades CS.

Cancer Res. 2009 Jul 15;69(14):5835-42. doi: 10.1158/0008-5472.CAN-08-4285. Epub 2009 Jul 7.


Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors.

Marone R, Erhart D, Mertz AC, Bohnacker T, Schnell C, Cmiljanovic V, Stauffer F, Garcia-Echeverria C, Giese B, Maira SM, Wymann MP.

Mol Cancer Res. 2009 Apr;7(4):601-13. doi: 10.1158/1541-7786.MCR-08-0366.


Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition.

Breuleux M, Klopfenstein M, Stephan C, Doughty CA, Barys L, Maira SM, Kwiatkowski D, Lane HA.

Mol Cancer Ther. 2009 Apr;8(4):742-53. doi: 10.1158/1535-7163.MCT-08-0668.


Discovery of novel anticancer therapeutics targeting the PI3K/Akt/mTOR pathway.

Maira SM, Furet P, Stauffer F.

Future Med Chem. 2009 Apr;1(1):137-55. doi: 10.4155/fmc.09.5. Review.


Activity of a novel, dual PI3-kinase/mTor inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts.

Cao P, Maira SM, García-Echeverría C, Hedley DW.

Br J Cancer. 2009 Apr 21;100(8):1267-76. doi: 10.1038/sj.bjc.6604995. Epub 2009 Mar 24.


mTOR inhibitor RAD001 (everolimus) has antiangiogenic/vascular properties distinct from a VEGFR tyrosine kinase inhibitor.

Lane HA, Wood JM, McSheehy PM, Allegrini PR, Boulay A, Brueggen J, Littlewood-Evans A, Maira SM, Martiny-Baron G, Schnell CR, Sini P, O'Reilly T.

Clin Cancer Res. 2009 Mar 1;15(5):1612-22. doi: 10.1158/1078-0432.CCR-08-2057. Epub 2009 Feb 17.


PI3K and mTOR inhibitors: a new generation of targeted anticancer agents.

Brachmann S, Fritsch C, Maira SM, García-Echeverría C.

Curr Opin Cell Biol. 2009 Apr;21(2):194-8. doi: 10.1016/ Epub 2009 Feb 7. Review.


PI3K inhibitors for cancer treatment: where do we stand?

Maira SM, Stauffer F, Schnell C, García-Echeverría C.

Biochem Soc Trans. 2009 Feb;37(Pt 1):265-72. doi: 10.1042/BST0370265. Review.


The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations.

Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, García-Echeverría C, Schultz PG, Reddy VA.

Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):268-73. doi: 10.1073/pnas.0810956106. Epub 2008 Dec 30.


Respiratory epithelial adenomatoid hamartoma: case report and literature review.

Caltabiano R, Cocuzza S, Maira S, Gurrera A, Serra A, Lanzafame S.

Pathologica. 2008 Jun;100(3):185-8. Review.


PTEN-deficient cancers depend on PIK3CB.

Wee S, Wiederschain D, Maira SM, Loo A, Miller C, deBeaumont R, Stegmeier F, Yao YM, Lengauer C.

Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13057-62. doi: 10.1073/pnas.0802655105. Epub 2008 Aug 28.


Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging.

Schnell CR, Stauffer F, Allegrini PR, O'Reilly T, McSheehy PM, Dartois C, Stumm M, Cozens R, Littlewood-Evans A, García-Echeverría C, Maira SM.

Cancer Res. 2008 Aug 15;68(16):6598-607. doi: 10.1158/0008-5472.CAN-08-1044.


Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity.

Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chène P, De Pover A, Schoemaker K, Fabbro D, Gabriel D, Simonen M, Murphy L, Finan P, Sellers W, García-Echeverría C.

Mol Cancer Ther. 2008 Jul;7(7):1851-63. doi: 10.1158/1535-7163.MCT-08-0017. Epub 2008 Jul 7.


[Detection of gastric preneoplastic lesions with serum levels of pepsinogen in Chilean subjects].

Fernández F JI, de Aretxabala U X, Santander D R, Sabah T S, Maira S J, Navarro R A, Planzer D M, Gómez L F, Etchart M, Gallegos I, Torrens X, Fasce P G, Reydet I.

Rev Med Chil. 2007 Dec;135(12):1519-25. doi: /S0034-98872007001200003. Epub 2008 Feb 13. Spanish.


Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway.

Stauffer F, Maira SM, Furet P, García-Echeverría C.

Bioorg Med Chem Lett. 2008 Feb 1;18(3):1027-30. doi: 10.1016/j.bmcl.2007.12.018. Epub 2007 Dec 15.


Class IA phosphatidylinositol 3-kinase: from their biologic implication in human cancers to drug discovery.

Maira SM, Voliva C, Garcia-Echeverria C.

Expert Opin Ther Targets. 2008 Feb;12(2):223-38. doi: 10.1517/14728222.12.2.223 . Review.


Patupilone (epothilone B, EPO906) and imatinib (STI571, Glivec) in combination display enhanced antitumour activity in vivo against experimental rat C6 glioma.

O'Reilly T, Wartmann M, Maira SM, Hattenberger M, Vaxelaire J, Muller M, Ferretti S, Buchdunger E, Altmann KH, McSheehy PMJ.

Cancer Chemother Pharmacol. 2005 Apr;55(4):307-317. doi: 10.1007/s00280-004-0913-z. Epub 2004 Oct 26.


The transcription factor Net regulates the angiogenic switch.

Zheng H, Wasylyk C, Ayadi A, Abecassis J, Schalken JA, Rogatsch H, Wernert N, Maira SM, Multon MC, Wasylyk B.

Genes Dev. 2003 Sep 15;17(18):2283-97.

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