Novel in-Vitro and in-Vivo Strategies to Study Pancreatic Ductal Adenocarcinoma Progression and Chemoresistance

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Background

Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancers and is one of the major cause of deaths with a five-year survival rate below 10 %. PDAC is characterized by extensive desmoplasia with cancer associated fibroblasts (CAF’s), pancreatic stellate cells, heavy immune cell infiltration and chemo resistant cancer stem cells often barriers to the treatment. The acinar cells of the pancreas were reported to transdifferentiate and acquire a ductal like phenotype under environmental (inflammation) and/or oncogenic (mutations) stress leading to development of precursor lesions (PanINs) sensitive to further oncogenic insults and transformation to invasive carcinoma. Currently, there are only a few drugs approved by FDA which offer a modest benefit to patients exposing the gaps in our knowledge to completely understand the complex nature of the disease and multitude of factors involved. Chemotherapy such as gemcitabine is considered the standard of care for most patients diagnosed with advanced PDAC. Unfortunately, development of gemcitabine resistance was observed in most patients within the first few weeks of treatment. Therefore, there is urgent need to understand both intrinsic and extrinsic factors that facilitate the development of chemoresistance in PDAC.

Earlier studies revealed mutant KRAS, TP53, SMAD4 and CDNK2A as key genomic drivers for PDAC growth and metastasis. However, the efforts to directly target these driver mutations have not been successful and are still explored. It is critical to identify novel targets to develop effective treatment strategies that could improve the patient outcomes. Multiple invitro 2D cell culture /3D organoid models and in vivo- genetically engineered mouse models (GEMM’s) have helped us to gain some insight into the disease, however, further research can aid to fully understand the pathogenesis and the therapeutic response of PDAC for the development of successful therapies.

In this research topic we invite authors to submit reviews or original work that focus on understanding the pathogenesis of PDAC and novel treatment strategies including immunotherapies to target chemo resistant tumor cells. Basic, translational, and Clinical research articles are highly encouraged.

Potential topics included but are not limited to the following.

a) Mechanism of progression from PanINs to PDAC

b) Biomarkers associated with PanIN to PDAC progression

c) Role of novel proteins in PDAC growth and metastasis

d) New treatment strategies both chemo/immunotherapies to target PDAC

e) Role of Cancer stem cells in PDAC progression

f) Role of tumor microenvironment in PDAC growth and metastasis

g) Invitro/In vivo models to study chemoresistance of PDAC tumor cells

Keywords: pancreatic cancer, chemoresistance

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