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Bcl-2/Bcl-xL inhibition increases the efficacy of MEK inhibition alone and in combination with PI3 kinase inhibition in lung and pancreatic tumor models.

Tan N, Wong M, Nannini MA, Hong R, Lee LB, Price S, Williams K, Savy PP, Yue P, Sampath D, Settleman J, Fairbrother WJ, Belmont LD.

Mol Cancer Ther. 2013 Jun;12(6):853-64. doi: 10.1158/1535-7163.MCT-12-0949. Epub 2013 Mar 8.


Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition.

Hoeflich KP, Merchant M, Orr C, Chan J, Den Otter D, Berry L, Kasman I, Koeppen H, Rice K, Yang NY, Engst S, Johnston S, Friedman LS, Belvin M.

Cancer Res. 2012 Jan 1;72(1):210-9. doi: 10.1158/0008-5472.CAN-11-1515. Epub 2011 Nov 14.


The Mutant KRAS Gene Up-regulates BCL-XL Protein via STAT3 to Confer Apoptosis Resistance That Is Reversed by BIM Protein Induction and BCL-XL Antagonism.

Zaanan A, Okamoto K, Kawakami H, Khazaie K, Huang S, Sinicrope FA.

J Biol Chem. 2015 Sep 25;290(39):23838-49. doi: 10.1074/jbc.M115.657833. Epub 2015 Aug 5.


Modeling targeted inhibition of MEK and PI3 kinase in human pancreatic cancer.

Junttila MR, Devasthali V, Cheng JH, Castillo J, Metcalfe C, Clermont AC, Otter DD, Chan E, Bou-Reslan H, Cao T, Forrest W, Nannini MA, French D, Carano R, Merchant M, Hoeflich KP, Singh M.

Mol Cancer Ther. 2015 Jan;14(1):40-7. doi: 10.1158/1535-7163.MCT-14-0030. Epub 2014 Nov 5.


The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells.

Zou ZQ, Zhang LN, Wang F, Bellenger J, Shen YZ, Zhang XH.

Mol Med Rep. 2012 Feb;5(2):503-8. doi: 10.3892/mmr.2011.682. Epub 2011 Nov 16.


[Growth inhibition of combined pathway inhibitors on KRAS mutated non-small cell lung cancer cell line].

Li ZW, Yang ZL, Feng HL, Bian XC, Liu YY, Liu YQ.

Zhonghua Bing Li Xue Za Zhi. 2013 May;42(5):330-5. doi: 10.3760/cma.j.issn.0529-5807.2013.05.009. Chinese.


Navitoclax enhances the efficacy of taxanes in non-small cell lung cancer models.

Tan N, Malek M, Zha J, Yue P, Kassees R, Berry L, Fairbrother WJ, Sampath D, Belmont LD.

Clin Cancer Res. 2011 Mar 15;17(6):1394-404. doi: 10.1158/1078-0432.CCR-10-2353. Epub 2011 Jan 10.


PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and mutant KRAS signaling.

Halilovic E, She QB, Ye Q, Pagliarini R, Sellers WR, Solit DB, Rosen N.

Cancer Res. 2010 Sep 1;70(17):6804-14. doi: 10.1158/0008-5472.CAN-10-0409. Epub 2010 Aug 10.


Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage.

Jokinen E, Koivunen JP.

Int J Oncol. 2015 Sep;47(3):1103-10. doi: 10.3892/ijo.2015.3071. Epub 2015 Jul 2.


Synergy between phosphatidylinositol 3-kinase/Akt pathway and Bcl-xL in the control of apoptosis in adenocarcinoma cells of the lung.

Qian J, Zou Y, Rahman JS, Lu B, Massion PP.

Mol Cancer Ther. 2009 Jan;8(1):101-9. doi: 10.1158/1535-7163.MCT-08-0973.


Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers.

Hata AN, Yeo A, Faber AC, Lifshits E, Chen Z, Cheng KA, Walton Z, Sarosiek KA, Letai A, Heist RS, Mino-Kenudson M, Wong KK, Engelman JA.

Cancer Res. 2014 Jun 1;74(11):3146-56. doi: 10.1158/0008-5472.CAN-13-3728. Epub 2014 Mar 27.


Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models.

Corcoran RB, Cheng KA, Hata AN, Faber AC, Ebi H, Coffee EM, Greninger P, Brown RD, Godfrey JT, Cohoon TJ, Song Y, Lifshits E, Hung KE, Shioda T, Dias-Santagata D, Singh A, Settleman J, Benes CH, Mino-Kenudson M, Wong KK, Engelman JA.

Cancer Cell. 2013 Jan 14;23(1):121-8. doi: 10.1016/j.ccr.2012.11.007. Epub 2012 Dec 13.


Cotargeting MAPK and PI3K signaling with concurrent radiotherapy as a strategy for the treatment of pancreatic cancer.

Williams TM, Flecha AR, Keller P, Ram A, Karnak D, Galbán S, Galbán CJ, Ross BD, Lawrence TS, Rehemtulla A, Sebolt-Leopold J.

Mol Cancer Ther. 2012 May;11(5):1193-202. doi: 10.1158/1535-7163.MCT-12-0098. Epub 2012 Mar 12.


γ-Secretase inhibition promotes cell death, Noxa upregulation, and sensitization to BH3 mimetic ABT-737 in human breast cancer cells.

Séveno C, Loussouarn D, Bréchet S, Campone M, Juin P, Barillé-Nion S.

Breast Cancer Res. 2012 Jun 15;14(3):R96.


Navitoclax (ABT-263) accelerates apoptosis during drug-induced mitotic arrest by antagonizing Bcl-xL.

Shi J, Zhou Y, Huang HC, Mitchison TJ.

Cancer Res. 2011 Jul 1;71(13):4518-26. doi: 10.1158/0008-5472.CAN-10-4336. Epub 2011 May 5.


Roles of BIM induction and survivin downregulation in lapatinib-induced apoptosis in breast cancer cells with HER2 amplification.

Tanizaki J, Okamoto I, Fumita S, Okamoto W, Nishio K, Nakagawa K.

Oncogene. 2011 Sep 29;30(39):4097-106. doi: 10.1038/onc.2011.111. Epub 2011 Apr 18.


PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD.

Pareja F, Macleod D, Shu C, Crary JF, Canoll PD, Ross AH, Siegelin MD.

Mol Cancer Res. 2014 Jul;12(7):987-1001. doi: 10.1158/1541-7786.MCR-13-0650. Epub 2014 Apr 22.


BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors.

Korfi K, Smith M, Swan J, Somervaille TC, Dhomen N, Marais R.

Cell Death Dis. 2016 Apr 7;7:e2177. doi: 10.1038/cddis.2016.70.

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