Recent Update of Molecular Targeted Therapy in Pancreatic Cancer

Jae Hee Cho

doi:10.4166/kjg.2013.61.3.147

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Cho: Recent Update of Molecular Targeted Therapy in Pancreatic Cancer

Review Article

Korean J Gastroenterol 2013;61(3):147-154.

Published online: 4 October 2013

DOI: https://doi.org/10.4166/kjg.2013.61.3.147

Recent Update of Molecular Targeted Therapy in Pancreatic Cancer

Jae Hee Cho

Division of Gastroenterology, Myongji Hospital, Department of Internal Medicine, Kwandong University College of Medicine, Korea

Correspondence to: Jae Hee Cho, Division of Gastroenterology, Myongji Hospital, Department of Internal Medicine, Kwandong University College of Medicine, 697-24 Hwajeong-dong, Deogyang-gu, Goyang 412-270, Korea. Tel: +82-31-810-5431, Fax: +82-31-810-7002, E-mail: jhcho932@kd.ac.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Pancreatic ductal adenocarcinoma is one of the most dreaded malignancies and the 5th leading cause of cancer-related death in Korea. Late diagnosis and unfavorable response to both chemotherapy and radiotherapy result in exceptionally poor prognosis. Recently, the rapid advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis, and there are many attempts to modulate signal pathway using specific targeted agent. However, the most of them have so far failed to improve survival significantly except erlotinib. The real challenge is now how these impressive advances of molecular biology could be successfully integrated into better clinical implications. Herein, we summarize the latest insights into the carcinogenesis, and their repercussions for novel targeted agents for pancreatic cancer, and provide a review of recent clinical trials using molecular targeted therapy.

Keywords: Pancreatic neoplasms, Molecular targeted therapy

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Fig. 1.

Schematic overview of major survival and proliferation signal pathways and molecular targeted agents currently evaluated in pancreatic cancer. RTK, receptor tyrosine kinase; Grb2, growth factor receptor bound protein 2; SOS, sons of sevenless homolog; MEK, mitogen activated pro-tein/extracellular signal regulated kinase kinase; ERK, extracellular signal regulated kinase; PI3K, phosphoinositide 3-kinase; PTEN, phosphatase and tensin homologue; mTOR, mammalian target of rapamycin; S6K1, S6 kinase 1; 4EBP, 4E binding protein; IGF-1R, insulin-like growth factor-1 receptor; VEGF, vascular endothelial growth factor; HIF, hypoxia inducible factor.

Table 1.

Results of Phase III Trials of Molecular Targeted Agents in Advanced/Metastatic Pancreatic Cancer

Target	Series	Regimen	Number	Median survival (month)	p-value
MMP	Bramhall et al. (2002)⁴⁹	Marimastat＋ Gem	120	5.4	0.99
		Gem	119	5.4
FT	Van Cutsem et al. (2004)²⁵	Tipifarnib＋ Gem	341	5.9	0.75
		Gem	347	6.3
EGFR	Moore et al. (2007)⁵	Erlotinib＋ Gem	285	6.2	0.03
		Gem	284	5.9
EGFR, VEGF	Van Cutsem et al. (2009)¹⁶	Bevacizumab＋ erlotinib＋ Gem	306	7.1	0.21
		Erlotinib＋ Gem	301	6.0
VEGF	Kindler et al. (2010)¹⁵	Bevacizumab＋ Gem	302	5.8	0.95
		Gem	300	5.9
EGFR	Philip et al. (2010)¹¹	Cetuximab＋ Gem	362	6.3	0.23
		Gem	357	5.9
VEGF	Kindler et al. (2011)¹⁷	Axitinib＋ Gem	314	8.5	0.54
		Gem	316	8.3
VEGF, B-Raf, PDGFR	R-B Gonçalves et al. (2012)¹⁸	Sorafenib＋ Gem	52	8.0	0.23
		Gem	52	9.2

MMP, matrix metalloproteinase; FT, farnesyl transferase; EGFR, epidermal growth factor receptor; VEGF, vascular endothelial growth factor; PDGFR-B, platelet derived growth factor receptor-B; Gem, gemcitabine.

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