Annual Meeting of the Canadian Association of Medical Oncology
Title: In vitro combination of histone deacetylase and proteasome inhibition on pancreatic and hepatocellular cancer cell lines: antiproliferative, pro-apoptotic, and metabolic effects.
Authors: J.L. Spratlin1, T.M. Pitts1, J.J. Tentler1, N.J. Serkova2, S.G. Eckhardt1. University of Colorado at Denver and Health Sciences Center, 1Division of Medical Oncology, 2Department of Anesthesiology, Aurora, CO, USA.
Pitts, T.M., Morrow, M., Kaufman, S.A., Tentler, J.J., Eckhardt, S.G. Vorinostat and Bortezomib Exert Synergistic Anti-proliferative and Pro-apoptotic Effects in Colon Cancer Cell Models 2009. Molecular Cancer Therapeutics 8:342-349.
Tentler JJ, Bradshaw-Pierce EL, Serkova NJ, Hasebroock KM, Pitts TM, Diamond JR, Fletcher GC, Bray MR, Eckhardt SG. Assessment of the in vivo antitumor effects of ENMD-2076, a novel multitargeted kinase inhibitor, against primary and cell line-derived human colorectal cancer xenograft models. Clin Cancer Res. 2010;16(11):2989-98.
Pitts TM, Tan AC, Kulikowski GN, Tentler JJ, Brown AM Flanigan SA, Leong S, Coldren C, Hirsch FR Varella-Garcia M, Korch C, Eckhardt SG. Development of an Integrated Genomic Classifier for a Novel Agent in Colorectal Cancer: Approach to Individualized Therapy in Early Development Clin Cancer Res 2010;16(12):3193-204.
Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, Arcaroli JJ, Messersmith WA, Eckhardt SG. Patient-derived tumour xenografts as models for oncology drug development. Nature Reviews Clinical Oncology 2012 9(6):338-350
Sullivan KD, Padilla-Just N, Henry RE, Porter CC, Kim J, Tentler JJ, Eckhardt SG, Tan AC, DeGregori J, Espinosa JM. ATM and MET kinases are synthetic lethal with non-genotoxic activation of p53. Nature Chemical Biology. 2012 8(7): 646–654.
Diamond JR, Eckhardt SG, Tan AC, Newton TP, Selby HM, Brunkow KL, Kachaeva MI, Garcia MV, Pitts TM, Bray MR, Fletcher GC, Tentler JJ. Predictive biomarkers of sensitivity to the aurora and angiogenic kinase inhibitor ENMD-2076 in preclinical breast cancer models. Clin Cancer Res. 2013 Jan 1;19(1):291-303
Deng H, Liu J, Deng Y, Han G, Shellman YG, Robinson SE, Tentler JJ, Robinson WA, Norris DA, Wang XJ, Zhang Q. CtBP1 Is Expressed in Melanoma and Represses the Transcription of p16INK4a and Brca1. Journal of Investigative Dermatolology. 2013 Jan 10 epub ahead of print
Diamond JR, Eckhardt SG, Tan AC, Newton TP, Selby HM, Brunkow, KL, Kachaeva MI, Garcia MV,
Pitts TM, Bray MR, Fletcher GC, Tentler JJ. Predictive biomarkers of sensitivity to the aurora and angiogenic
kinase inhibitor ENMD-2076 in preclinical breast cancer models. Clin Cancer Res. 2013 Jan 1;19(1):291-303.
Tan, AC, Leong, S, Pitts, TM, Tentler, JJ, Eckhardt, SG. New Approaches to Integration of Personalized
Medicine in Early Cancer Drug Development. In: Principles of Molecular Diagnostics and Personalized Cancer Medicine.
D. Tan and HT Lynch, Eds. Lippincott Williams and Williams 2013 659-673.
Deng H, Liu J, Deng Y, Han G, Shellman YG, Robinson SE, Tentler JJ, Robinson WA, Norris DA, Wang XJ,
Zhang Q. CtBP1 Is Expressed in Melanoma and Represses the Transcription of p16INK4a and Brca1.
J Invest Dermatol. 2013 133:1294-301.
Micel LN, Tentler JJ, Smith PG, Eckhardt SG. Role of Ubiquitin Ligases and the Proteasome in Oncogenesis:
Novel Targets for Anticancer Therapies. J Clin Oncol. 2013 31:1231-8. Featured on Cover of this Issue
Schlegel J, Sambade MJ, Sather S, Moschos SJ, Tan AC, Winges A, DeRyckere D, Carson CC, Trembath DG, Tentler JJ, Eckhardt SG, Kuan PF, Hamilton RL, Duncan LM, Miller CR, Nikolaishvili-Feinberg N, Midkiff BR, Liu J, Zhang W, Yang C, Wang X, Frye SV, Earp HS, Shields JM, Graham DK. MERTK receptor tyrosine kinase is a therapeutic target in melanoma. J Clin Invest. 2013 123(5):2257-67.
Micel LN, Tentler JJ, Smith PG, Eckhardt SG. Role of Ubiquitin Ligases and the Proteasome in Oncogenesis: Novel Targets for Anticancer Therapies. J Clin Oncol. 2013 Jan 28. epub ahead of print
Pitts TM, Kulikowski GN, Tan AC, Murray BW, Arcaroli JJ, Tentler JJ, Spreafico A, Selby HM, Kachaeva MI, McPhillips KL, Britt BC, Bradshaw-Pierce EL, Messersmith WA, Varella-Garcia M, Eckhardt SG. Association of the Epithelial-to-Mesenchymal Transition (EMT) Phenotype with Responsiveness to the p21-Activated Kinase Inhibitor, PF-3758309, in Colon Cancer Models. Frontiers in Pharmacology of Anti-Cancer Drugs. 2013 epub ahead of print
Pitts TM, Kulikowski GN, Tan AC, Murray BW, Arcaroli JJ, Tentler JJ, Spreafico A, Selby HM, Kachaeva MI, McPhillips KL, Britt BC, Bradshaw-Pierce EL, Messersmith WA, Varella-Garcia M, Eckhardt SG.
Association of the epithelial-to-mesenchymal transition phenotype with responsiveness to the p21-activated kinase inhibitor, PF-3758309, in colon cancer models. Front Pharmacol. 2013 4:35.
Schlegel J, Sambade MJ, Sather S, Moschos MJ, Tan AC, Winges A, DeRyckere D, Carson CC, Trembath DG, Tentler JJ, Eckhardt SG, Kuan PF, Hamilton RL,. Duncan LM, Alldredge V, Groben PA, Ollila DW, Thomas NE, Wang X, Frye SV, Earp HS,. Shields JM, Graham DK. Mer Receptor Tyrosine Kinase is Novel Therapeutic Target in Melanoma. Journal of Clinical Investigation. 2013 epub ahead of print
Spreafico A, Tentler JJ, Pitts TM, Tan AC, Gregory MA, Arcaroli JJ, Klauck PJ, McManus MC, Hansen RJ, Kim J, Micel LN, Selby HM, Newton TP, McPhillips K, Gustafson DL, DeGregori JV, Messersmith WA, Winn RA, Eckhardt SG. Rational Combination of a MEK Inhibitor, Selumetinib, and the Wnt/Calcium Pathway Modulator, Cyclosporin A, in Preclinical Models of Colorectal Cancer. Clin Cancer Res. 2013 19(15):4149-62.
Turner J, Couts K, Sheren J, Saichaemchan S, Ariyawutyakorn W, Avolio I, Cabral E, Glogowska M, Amato C, Robinson S, Hintzsche J, Applegate A, Seelenfreund E, Gonzalez R, Wells K, Bagby S, Tentler J, Tan AC, Wisell J, Varella-Garcia M, Robinson W. Kinase gene fusions in defined subsets of melanoma. Pigment Cell Melanoma Res. 2017 Jan;30(1):53-62. PubMed PMID: 27864876
Klauck PJ, Bagby SM, Capasso A, Bradshaw-Pierce EL, Selby HM, Spreafico A, Tentler JJ, Tan AC, Kim J, Arcaroli JJ, Purkey A, Messersmith WA, Kuida K, Gail Eckhardt S, Pitts TM. Antitumor activity of the polo-like kinase inhibitor, TAK-960, against preclinical models of colorectal cancer. BMC Cancer. 2018 Feb 5;18(1):136. PubMed PMID: 29402316
Wong KM, Micel LN, Selby HM, Tan AC, Pitts TM, Bagby SM, Spreafico A, Klauck PJ, Blakemore SJ, Smith PF, McDonald A, Berger A, Tentler JJ, Eckhardt SG. Targeting the protein ubiquitination machinery in melanoma by the NEDD8-activating enzyme inhibitor pevonedistat (MLN4924). Invest New Drugs. 2017 Feb;35(1):11-25. PubMed PMID: 27783255
Couts KL, Bemis J, Turner JA, Bagby SM, Murphy D, Christiansen J, Hintzsche JD, Le A, Pitts TM, Wells K, Applegate A, Amato C, Multani P, Chow-Maneval E, Tentler JJ, Shellman YG, Rioth MJ, Tan AC, Gonzalez R, Medina T, Doebele RC, Robinson WA. ALK Inhibitor Response in Melanomas Expressing EML4-ALK Fusions and Alternate ALK Isoforms. Mol Cancer Ther. 2018 Jan;17(1):222-231. PubMed PMID: 29054983
Ionkina AA, Tentler JJ, Kim J, Capasso A, Pitts TM, Ryall KA, Howison RR, Kabos P, Sartorius CA, Tan AC, Eckhardt SG, Diamond JR. Efficacy and Molecular Mechanisms of Differentiated Response to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Models of p53-Mutated Triple-Negative Breast Cancer. Front Oncol. 2017;7:94. PubMed PMID: 28555173
Bagby S, Messersmith WA, Pitts TM, Capasso A, Varella-Garcia M, Klauck PJ, Kim J, Tan AC, Eckhardt SG, Tentler JJ, Arcaroli J. Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies. J Vis Exp. 2016 Sep 30;(115). PubMed PMID: 27768028
Hintzsche JD, Gorden NT, Amato CM, Kim J, Wuensch KE, Robinson SE, Applegate AJ, Couts KL, Medina TM, Wells KR, Wisell JA, McCarter MD, Box NF, Shellman YG, Gonzalez RC, Lewis KD, Tentler JJ, Tan AC, Robinson WA. Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma. Melanoma Res. 2017 Jun;27(3):189-199. PubMed PMID: 28296713
Turner J, Couts K, Sheren J, Saichaemchan S, Ariyawutyakorn W, Avolio I, Cabral E, Glogowska M, Amato C, Robinson S, Hintzsche J, Applegate A, Seelenfreund E, Gonzalez R, Wells K, Bagby S, Tentler J, Tan AC, Wisell J, Varella-Garcia M, Robinson W. Kinase gene fusions in defined subsets of melanoma. Pigment Cell Melanoma Res. 2017 Jan;30(1):53-62. PubMed PMID: 27864876
Wong KM, Micel LN, Selby HM, Tan AC, Pitts TM, Bagby SM, Spreafico A, Klauck PJ, Blakemore SJ, Smith PF, McDonald A, Berger A, Tentler JJ, Eckhardt SG. Targeting the protein ubiquitination machinery in melanoma by the NEDD8-activating enzyme inhibitor pevonedistat (MLN4924). Invest New Drugs. 2017 Feb;35(1):11-25. PubMed PMID: 27783255
Pitts TM, Bradshaw-Pierce EL, Bagby SM, Hyatt SL, Selby HM, Spreafico A, Tentler JJ, McPhillips K, Klauck PJ, Capasso A, Diamond JR, Davis SL, Tan AC, Arcaroli JJ, Purkey A, Messersmith WA, Ecsedy JA, Eckhardt SG. Antitumor activity of the aurora a selective kinase inhibitor, alisertib, against preclinical models of colorectal cancer. Oncotarget. 2016 Aug 2;7(31):50290-50301. PubMed PMID: 27385211
Hintzsche J, Kim J, Yadav V, Amato C, Robinson SE, Seelenfreund E, Shellman Y, Wisell J, Applegate A, McCarter M, Box N, Tentler J, De S, Robinson WA, Tan AC. IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples. J Am Med Inform Assoc. 2016 Jul;23(4):721-30. PubMed PMID: 27026619
Capasso A, Bagby SM, Dailey KL, Currimjee N, Yacob BW, Ionkina A, Frank JG, Kim DJ, George C, Lee YB, Benaim E, Gittleman B, Hartman SJ, Tan AC, Kim J, Pitts TM, Eckhardt SG, Tentler JJ, Diamond JR. First-in-Class Phosphorylated-p68 Inhibitor RX-5902 Inhibits ß-Catenin Signaling and Demonstrates Antitumor Activity in Triple-Negative Breast Cancer. Mol Cancer Ther. 2019 Nov;18(11):1916-1925. PubMed PMID: 31488700
Sinik L, Minson KA, Tentler JJ, Carrico J, Bagby SM, Robinson WA, Kami R, Burstyn-Cohen T, Eckhardt SG, Wang X, Frye SV, Earp HS, DeRyckere D, Graham DK. Inhibition of MERTK Promotes Suppression of Tumor Growth in BRAF Mutant and BRAF Wild-Type Melanoma. Mol Cancer Ther. 2019 Feb;18(2):278-288. PubMed PMID: 30482852
Turner JA, Bemis JGT, Bagby SM, Capasso A, Yacob BW, Chimed TS, Van Gulick R, Lee H, Tobin R, Tentler JJ, Pitts T, McCarter M, Robinson WA, Couts KL. BRAF fusions identified in melanomas have variable treatment responses and phenotypes. Oncogene. 2019 Feb;38(8):1296-1308. PubMed PMID: 30254212
Tentler JJ, Lang J, Capasso A, Kim DJ, Benaim E, Lee YB, Eisen A, Bagby SM, Hartman SJ, Yacob BW, Gittleman B, Pitts TM, Pelanda R, Eckhardt SG, Diamond JR. RX-5902, a novel ß-catenin modulator, potentiates the efficacy of immune checkpoint inhibitors in preclinical models of triple-negative breast Cancer. BMC Cancer. 2020 Nov 4;20(1):1063. PubMed PMID: 33148223
Davis SL, Ionkina AA, Bagby SM, Orth JD, Gittleman B, Marcus JM, Lam ET, Corr BR, O'Bryant CL, Glode AE, Tan AC, Kim J, Tentler JJ, Capasso A, Lopez KL, Gustafson DL, Messersmith WA, Leong S, Eckhardt SG, Pitts TM, Diamond JR. Preclinical and Dose-Finding Phase I Trial Results of Combined Treatment with a TORC1/2 Inhibitor (TAK-228) and Aurora A Kinase Inhibitor (Alisertib) in Solid Tumors. Clin Cancer Res. 2020 Sep 1;26(17):4633-4642. PubMed PMID: 32414750
Pitts TM, Simmons DM, Bagby SM, Hartman SJ, Yacob BW, Gittleman B, Tentler JJ, Cittelly D, Ormond DR, Messersmith WA, Eckhardt SG, Diamond JR. Wee1 Inhibition Enhances the Anti-Tumor Effects of Capecitabine in Preclinical Models of Triple-Negative Breast Cancer. Cancers (Basel). 2020 Mar 19;12(3). PubMed PMID: 32204315
Diamond JR, Pitts TM, Ungermannova D, Nasveschuk CG, Zhang G, Phillips AJ, Bagby SM, Pafford J, Yacob BW, Newton TP, Tentler JJ, Gittleman B, Hartman SJ, DeMattei JA, Winkler JD, Wendt MK, Schiemann WP, Eckhardt SG, Liu X, Piscopio AD. Preclinical development of the class I selective histone deacetylase inhibitor OKI-179 for the treatment of solid tumors. Mol Cancer Ther. 2021 Dec 29. [Epub ahead of print] PubMed PMID: 34965958
Hartman SJ, Bagby SM, Yacob BW, Simmons DM, MacBeth M, Lieu CH, Davis SL, Leal AD, Tentler JJ, Diamond JR, Eckhardt SG, Messersmith WA, Pitts TM. WEE1 Inhibition in Combination With Targeted Agents and Standard Chemotherapy in Preclinical Models of Pancreatic Ductal Adenocarcinoma. Front Oncol. 2021;11:642328. PubMed PMID: 33869031
Diamond JR, Pitts TM, Ungermannova D, Nasveschuk CG, Zhang G, Phillips AJ, Bagby SM, Pafford J, Yacob BW, Newton TP, Tentler JJ, Gittleman B, Hartman SJ, DeMattei JA, Winkler JD, Wendt MK, Schiemann WP, Eckhardt SG, Liu X, Piscopio AD. Preclinical Development of the Class-I-Selective Histone Deacetylase Inhibitor OKI-179 for the Treatment of Solid Tumors. Mol Cancer Ther. 2022 Mar 1;21(3):397-406. PubMed PMID: 34965958