Molecular Alterations in Pancreatic Cancer: Transfer to the Clinic

Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the exocrine pancreas and probably the tumor that has benefited the least from clinical progress in the last three decades. A consensus has been reached regarding the histologic classification of the ductal preneoplastic lesions (pa...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-02, Vol.22 (4), p.2077
Main Authors: Rodríguez Gil, Yolanda, Jiménez Sánchez, Paula, Muñoz Velasco, Raúl, García García, Ana, Sánchez-Arévalo Lobo, Víctor Javier
Format: Article
Language:English
Subjects:
Cancer therapies
Cell cycle
DNA repair
Epigenesis, Genetic
Genes
Genetic Heterogeneity
Genetic Predisposition to Disease
Humans
Medical prognosis
Metabolism
Molecular Targeted Therapy
Mutation
Pancreatic cancer
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
Pancreatitis
Review
Signal transduction
Translational Research, Biomedical
Tumors
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Summary:Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the exocrine pancreas and probably the tumor that has benefited the least from clinical progress in the last three decades. A consensus has been reached regarding the histologic classification of the ductal preneoplastic lesions (pancreatic intra-epithelial neoplasia-PanIN) and the molecular alterations associated with them. Mutations in and inactivation of , and are among the most prevalent alterations. Next generation sequencing studies are providing a broad picture of the enormous heterogeneity in this tumor type, describing new mutations less prevalent. These studies have also allowed the characterization of different subtypes with prognostic value. However, all this knowledge has not been translated into a clinical progress. Effective preventive and early diagnostic strategies are essential to improve the survival rates. The main challenge is, indeed, to identify new effective drugs. Despite many years of research and its limited success, gemcitabine is still the first line treatment of PDA. New drug combinations and new concepts to improve drug delivery into the tumor, as well as the development of preclinical predictive assays, are being explored and provide optimism and prospects for better therapies.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22042077