Pharmacogenomics in Pancreatic Adenocarcinoma: New Data and Their Clinical Implications
Abstract
Despite advances and investments in translation research, clinical trials and health service in general, there is no significant impact on the survival of most patients diagnosed with advanced pancreatic adenocarcinoma. It is broadly recognized though that there is a small minority of patients who really benefit from particular treatments for reason usually not well understood. Light to this fact is gradually shed by developments in the field of pharmacogenomics, which plays pivotal role in what we call individualized medicine. In that perspective, it is of most importance to present the significant developments in pharmacogenomics announced in the recent 2013 American Society of Clinical Oncology Annual Meeting. First, the predictive role of hENT1, which codes for a gemcitabine transporter into cells, was highlighted and might help us decide whether we benefit from gemcitabine or 5-fluorouracil in the adjuvant setting (Abstract #4006). Second, authors presented the negative predictive role of SPARC stroma and cytoplasmic expression in patients treated with adjuvant gemcitabine (within the CONCO-001 study) as they reported poor outcome of those having high expression, not seen in patients on observation (Abstract #4016). Finally, a study which might be a basis for future strategies and as great food for scientific thought suggested that selection of cytotoxic treatment based on gene expression profiling is feasible in clinical practice and may help improve treatment efficacy as well as predict for drug resistance (Abstract #4017). Of course, there is a long way to go before implementation of these genomic findings, with the exception of hENT1 which seems to be close for clinical use.
Image: Transport and metabolism of gemcitabine.
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References
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013 Jan;63(1):11-30.[PMID-23335087]
Giovannetti E, Del Tacca M, Mey V, Funel N, Nannizzi S, Ricci S, et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res 2006 Apr 1;66(7):3928-35. [PMID-16585222]
Marechal R, Bachet JB, Mackey JR, Dalban C, Demetter P, Graham K, et al. Levels of gemcitabine transport and metabolism proteins predict survival times of patients treated with gemcitabine for pancreatic adenocarcinoma. Gastroenterology 2012 Sep;143(3):664-74. [PMID-22705007]
Nakagawa N, Murakami Y, Uemura K, Sudo T, Hashimoto Y, Kondo N, et al. Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gemcitabine-based chemotherapy after operative resection. Surgery 2013 Apr;153(4):565-75. [PMID-23253379]
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011 May 12;364(19):1817-25. [PMID-21561347]
Von Hoff DD, Ervin TJ, Arena FP, Chiorean EG, Infante JR, Moore MJ, et al. Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT). J Clin Oncol (Meeting Abstracts) 2013 Jan 30;31(4_suppl):LBA148.
Neoptolemos JP, Greenhalf W, Ghaneh P, Palmer DH, Cox TF, Garner E, et al. HENT1 tumor levels to predict survival of pancreatic ductal adenocarcinoma patients who received adjuvant gemcitabine and adjuvant 5FU on the ESPAC trials. J Clin Oncol 2103; 31(Suppl.): Abstract #4006.
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer. N Engl J Med 2004 Mar 18;350(12):1200-10. [PMID- 15028824]
Neoptolemos J, Buchler M, Stocken DD, Ghaneh P, Smith D, Bassi C, et al. ESPAC-3(v2): A multicenter, international, open-label, randomized, controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma. J Clin Oncol (Meeting Abstracts) 2009 Jun 20;27(18S):LBA4505.
Sinn M, Sinn BV, Striefler JK, Stieler J, Pelzer U, Prinzler J, et al. SPARC in pancreatic cancer: Results from the CONKO-001 study. J Clin Oncol 2103; 31(Suppl.): Abstract #4016.
Yu KH, Sangar V, Ricigliano M, Hidalgo M, Abou-Alfa GK, Lowery MA, et al. Use of pharmacogenomic modeling in pancreatic cancer for prediction of chemotherapy response and resistance. J Clin Oncol 2103; 31(Suppl.): Abstract #4017.
Copyright (c) 2014 Alexios S Strimpakos, Kostas N Syrigos, Muhammad Wasif Saif
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