Molecular Alterations Involved in Pancreatic Cancer Chemoresistance and Chemosensitization Strategies

Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.

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Genetic Mutations of Pancreatic Cancer and Genetically Engineered Mouse Models

Cancers ◽

10.3390/cancers14010071 ◽

2021 ◽

Vol 14 (1) ◽

pp. 71

Author(s):

Yuriko Saiki ◽

Can Jiang ◽

Masaki Ohmuraya ◽

Toru Furukawa

Keyword(s):

Pancreatic Cancer ◽

Mouse Models ◽

Tumor Biology ◽

Genetically Engineered ◽

Lineage Tracing ◽

Ductal Adenocarcinoma ◽

Pancreatic Tumors ◽

Precursor Lesions ◽

Genetically Engineered Mouse Models ◽

Molecular Alterations

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.

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