Abstract
Current standard therapies for pancreatic ductal adenocarcinoma have failed to attenuate the aggressiveness of this disease or confer notable improvements in survival. Previous molecular research into pancreatic cancers, along with advances in sequencing technologies, have identified many altered genes in patients with pancreatic cancer and revealed the marked genetic heterogeneity of individual tumors. Thus, the lack of success of conventional empiric therapy can be partly attributed to the underlying heterogeneity of pancreatic tumors. The genetic alterations that have been detected in pancreatic cancer range from simple mutations at the level of base pairs to complex chromosomal structural changes and rearrangements. The identification of molecular changes that are unique to an individual patient's tumors, and the subsequent development of strategies to target the tumors in a personalized approach to therapeutics, is a necessary advance to improve therapy for patients with this disease.
Key Points
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Pancreatic cancer is a lethal malignancy; the treatment of patients with this disease is a therapeutic challenge
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Current therapies confer only modest increases in survival, often as little as a few months
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Molecular and genomic research into pancreatic cancer has demonstrated marked heterogeneity among tumors that might underlie differing responses to standard therapy
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Improved therapeutic outcomes might be realized in some patients through a personalized approach to targeting patient-specific genetic alterations in tumors
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Acknowledgements
N. Samuel is supported by an award from the Frank Fletcher Memorial Fund. T. J. Hudson is the recipient of a Senior Investigator Award from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.
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Samuel, N., Hudson, T. The molecular and cellular heterogeneity of pancreatic ductal adenocarcinoma. Nat Rev Gastroenterol Hepatol 9, 77–87 (2012). https://doi.org/10.1038/nrgastro.2011.215
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DOI: https://doi.org/10.1038/nrgastro.2011.215
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