Novel Agents for the Treatment of Pancreatic Cancer
Abstract
Metastatic pancreatic cancer continues to be a difficult disease to treat because of its aggressive nature, advanced stage at presentation and lack of treatment options. There is a need for the development of new agents directed against novel targets to improve outcomes for these patients. At the 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium phase I/II trials provided information on three novel strategies for treating metastatic pancreatic cancer. Immunotherapy in the form of a vaccine (GVAX) followed with an immune stimulator (CRS-207) showed extended survival (Abstract #177). A monoclonal antibody (NEO-102) targeting MUC5AC also showed activity and was well tolerated (Abstract #243). A heat shock protein 90 (HSP90) inhibitor (ganetespib) showed modest effects but was well tolerated making it available for use with conventional chemotherapy (Abstract #297). The details of these presentations will be discussed.
Image: University of Texas Southwestern Medical Center, Dallas, TX, USA
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References
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan; 63(1):11-30.
Dung T, Wang-Gillam A, Picozzi Jr V, Greten TF, Crocenzi TS, Springett GM, Morse M, Zeh H, Cohen DJ, Fine RL, Onmers B, et al. A phase 2, randomized trial of GVAX pancreas and CRS-207 immunotherapy versus GVAX alone in patients with metastatic pancreatic adenocarcinoma: Updated results. J Clin Oncol, 2014;32(suppl 3):Abstract 177.
Patel SP, Morse M, Beg MS, Azad NS, Beaston MA, Mavroukakis S, Arlen PM. J Clin Oncol 2014;32(suppl 3):Abstract 243.
Bafna S, Kaur S, Batra SK. Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells. Oncogene. 2010;29:2893-2904.
Takikita M, Altekruse S, Lynch CF, Goodman MT, Hernandez BY, Green M, Cozen W, Cockburn M, et al. Associations between selected biomarkers and prognosis in a population-based pancreatic cancer tissue microarray. Cancer Res 2009;69:2950-55.
Inaguma S, Kasai K, Ikeda H. Gl11 facilitates the migration and invasion of pancreatic cancer cells theough MUC5AC-mediated attenuation of E-cahedrin. Oncoge 2011;30:714-23.
Patel SP, Bristol A, Saric O, Wang X-P, Dubeykovskiy A, Arlen PM, Morse MA. Anti-tumor activity of a novel monoclonal antibody, NPC-1C, optimized for recognition of tumor antigen MUC5AC variant in preclinical models. Cancer Immunol Immunother 2013:62:1011-19.
Morse M, Diaz LA, Azad NS, Laheru D, Haley S, Sleer LS, Arlen PM. A phase Ib/IIa study of NEO-102: A therapeutic antibody to treat pancreatic and colorectal cancers. J Clin Oncol 2012;30(suppl 4):233.
Thota R, Goff LW, Chan E, Berlin J, Jones CM, McClanahan P, Ayers GD, Cardin DB. A phase II study of ganetespib (G) as second- or third-line therapy for metastatic pancreatic cancer (MPC). J Clin Oncol 2014;32(suppl 3):Abstract 297.
Choi HK, Lee K. Recent updates on the development of ganetespib as a HSP90 inhibitor. Arch Pharm Res 2012;35:1855-59.
Goldman JW, Raju RN, Gordon GA, El-Hariry I, Teofilivici F, Vukovic VM, Bradley R, Karol MD, Chen Y, Guo W, Inoue T, Rosen LS. A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the HSP90 inhibitor ganetespib (STA-9090) in patients with solid malignancies. BMC Cancer 2013;13:152-62.
Ying W, Du Z, Sun L, Foley KP, Proia DA, Blackman RK, Zhou D, Inoue T, Tatsuta N, Sang J, Ye S, Acquaviva J, Ogawa LS, Wada Y, Barsoum J, Koya K. Ganetespib, a unique triazolone-containing HSP90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther 2011;11(2):475-84.
Kauh JS, Harvey RD, Owonikoko TK, El-Rayes BF, Shin DM, Murali S, Lewis CM, Karol MD, Teofilovici F, Du Y, Fu H, Khuri FR, Ramalingam SS. A phase I and pharmacokinetic study of multiple schedules of ganetespib (STA-9090), a heat shock protein 90 inhibitor, in combination with docetaxel for subjects with advanced solid tumors malignancies. J Clin Oncol 2012 3094.
Copyright (c) 2014 Gregory T Brennan, Valerie Relias, Muhammad Wasif Saif
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