Abstract
Simple SummaryBased on the four molecular subtypes of pancreatic cancer described by Bailey et al. 2016, in the present article we match the molecular, histology and microenvironment features of pancreatic cancer. This approach may help to understand the molecular basis of this kind of tumor, and how their microenvironment may affect treatment response. Moreover, we compile information about crucial factors that could serve as potential targets for drug design to achieve higher anti-tumor activity, and how histological evaluation of tumor microenvironment could provide first signs about treatment response.In the last decade, several studies based on whole transcriptomic and genomic analyses of pancreatic tumors and their stroma have come to light to supplement histopathological stratification of pancreatic cancers with a molecular point-of-view. Three main molecular studies: Collisson et al. 2011, Moffitt et al. 2015 and Bailey et al. 2016 have found specific gene signatures, which identify different molecular subtypes of pancreatic cancer and provide a comprehensive stratification for both a personalized treatment or to identify potential druggable targets. However, the routine clinical management of pancreatic cancer does not consider a broad molecular analysis of each patient, due probably to the lack of target therapies for this tumor. Therefore, the current treatment decision is taken based on patients´ clinicopathological features and performance status. Histopathological evaluation of tumor samples could reveal many other attributes not only from tumor cells but also from their microenvironment specially about the presence of pancreatic stellate cells, regulatory T cells, tumor-associated macrophages, myeloid derived suppressor cells and extracellular matrix structure. In the present article, we revise the four molecular subtypes proposed by Bailey et al. and associate each subtype with other reported molecular subtypes. Moreover, we provide for each subtype a potential description of the tumor microenvironment that may influence treatment response according to the gene expression profile, the mutational landscape and their associated histology.
Highlights
Pancreatic cancer (PC) incidence has increased in developed countries and its trend for 2030 is to be higher reaching the second cause of cancer-related deaths [1]
Pancreatic cancer symptoms are often misdiagnosed and commonly treated ambulatory that leads to a late diagnosis with metastatic disease in distant organs; their 5-year survival rate decreased to 3% [3,4]
We review the four molecular subtypes of pancreatic cancer proposed by Bailey et al, and we used them as backbone to supplement their features with other PC molecular subtypes proposed by Moffitt et al, and Collisson et al we match each molecular subtype to a specific tumor histology and microenvironment, and how each complex network may influence treatment response
Summary
Pancreatic cancer (PC) incidence has increased in developed countries and its trend for 2030 is to be higher reaching the second cause of cancer-related deaths [1]. The infiltration of M2-polarized TAMs in PC stroma seems to be preferentially located in the body and tail of the pancreas, and with other TME cell populations, M2-polarized TAM confers shorter overall survival to patients [40] It has been reported how metformin could reduce desmoplasia of PC, reversion of epithelial-to-mesenchymal transition, and tumor-related inflammation via modulation of the AMPK/STAT3 that decreases levels of IL-1β and hampers infiltration of M2-polarized TAMs [41]. Since radiotherapy induces the release of lactate by tumor cells that lead to activation of MDSCs, a proposed treatment strategy would imply target lactate to increase radiotherapy response [50] Another mechanism described recently against MDSCs is by omega 3 administration due to its anti-inflammatory properties. We review the four molecular subtypes of pancreatic cancer proposed by Bailey et al, and we used them as backbone to supplement their features with other PC molecular subtypes proposed by Moffitt et al, and Collisson et al we match each molecular subtype to a specific tumor histology and microenvironment, and how each complex network may influence treatment response
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