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The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4.

Zang Y, Thomas SM, Chan ET, Kirk CJ, Freilino ML, DeLancey HM, Grandis JR, Li C, Johnson DE.

Autophagy. 2012 Dec;8(12):1873-4. doi: 10.4161/auto.22185.


Carfilzomib and ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy.

Zang Y, Thomas SM, Chan ET, Kirk CJ, Freilino ML, DeLancey HM, Grandis JR, Li C, Johnson DE.

Clin Cancer Res. 2012 Oct 15;18(20):5639-49. doi: 10.1158/1078-0432.CCR-12-1213.


Bortezomib induces autophagy in head and neck squamous cell carcinoma cells via JNK activation.

Li C, Johnson DE.

Cancer Lett. 2012 Jan 1;314(1):102-7. doi: 10.1016/j.canlet.2011.09.020.


Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells.

Li C, Li R, Grandis JR, Johnson DE.

Mol Cancer Ther. 2008 Jun;7(6):1647-55. doi: 10.1158/1535-7163.MCT-07-2444.


The novel β2-selective proteasome inhibitor LU-102 decreases phosphorylation of I kappa B and induces highly synergistic cytotoxicity in combination with ibrutinib in multiple myeloma cells.

Kraus J, Kraus M, Liu N, Besse L, Bader J, Geurink PP, de Bruin G, Kisselev AF, Overkleeft H, Driessen C.

Cancer Chemother Pharmacol. 2015 Aug;76(2):383-96. doi: 10.1007/s00280-015-2801-0.


The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib.

Milani M, Rzymski T, Mellor HR, Pike L, Bottini A, Generali D, Harris AL.

Cancer Res. 2009 May 15;69(10):4415-23. doi: 10.1158/0008-5472.CAN-08-2839.


The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects.

Hurchla MA, Garcia-Gomez A, Hornick MC, Ocio EM, Li A, Blanco JF, Collins L, Kirk CJ, Piwnica-Worms D, Vij R, Tomasson MH, Pandiella A, San Miguel JF, Garayoa M, Weilbaecher KN.

Leukemia. 2013 Feb;27(2):430-40. doi: 10.1038/leu.2012.183.


Mammalian target of rapamycin complex 1 (mTORC1) enhances bortezomib-induced death in tuberous sclerosis complex (TSC)-null cells by a c-MYC-dependent induction of the unfolded protein response.

Babcock JT, Nguyen HB, He Y, Hendricks JW, Wek RC, Quilliam LA.

J Biol Chem. 2013 May 31;288(22):15687-98. doi: 10.1074/jbc.M112.431056.


Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma.

Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ.

Blood. 2007 Nov 1;110(9):3281-90.


Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation.

Kao C, Chao A, Tsai CL, Chuang WC, Huang WP, Chen GC, Lin CY, Wang TH, Wang HS, Lai CH.

Cell Death Dis. 2014 Nov 6;5:e1510. doi: 10.1038/cddis.2014.468.


Interferon-γ-induced upregulation of immunoproteasome subunit assembly overcomes bortezomib resistance in human hematological cell lines.

Niewerth D, Kaspers GJ, Assaraf YG, van Meerloo J, Kirk CJ, Anderl J, Blank JL, van de Ven PM, Zweegman S, Jansen G, Cloos J.

J Hematol Oncol. 2014 Jan 13;7:7. doi: 10.1186/1756-8722-7-7.


Carfilzomib-dependent selective inhibition of the chymotrypsin-like activity of the proteasome leads to antitumor activity in Waldenstrom's Macroglobulinemia.

Sacco A, Aujay M, Morgan B, Azab AK, Maiso P, Liu Y, Zhang Y, Azab F, Ngo HT, Issa GC, Quang P, Roccaro AM, Ghobrial IM.

Clin Cancer Res. 2011 Apr 1;17(7):1753-64. doi: 10.1158/1078-0432.CCR-10-2130.


Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

Vogl DT, Stadtmauer EA, Tan KS, Heitjan DF, Davis LE, Pontiggia L, Rangwala R, Piao S, Chang YC, Scott EC, Paul TM, Nichols CW, Porter DL, Kaplan J, Mallon G, Bradner JE, Amaravadi RK.

Autophagy. 2014 Aug;10(8):1380-90. doi: 10.4161/auto.29264.


Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells.

Obeng EA, Carlson LM, Gutman DM, Harrington WJ Jr, Lee KP, Boise LH.

Blood. 2006 Jun 15;107(12):4907-16.


Advances in the understanding of mechanisms and therapeutic use of bortezomib.

Mujtaba T, Dou QP.

Discov Med. 2011 Dec;12(67):471-80. Review.


Anti-tumor activity of the proteasome inhibitor BSc2118 against human multiple myeloma.

Zang M, Li Z, Liu L, Li F, Li X, Dai Y, Li W, Kuckelkorn U, Doeppner TR, Hermann DM, Zhou W, Qiu L, Jin F.

Cancer Lett. 2015 Oct 1;366(2):173-81. doi: 10.1016/j.canlet.2015.06.011.

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