TY - JOUR
T1 - Fibroblasts in pancreatic cancer
T2 - molecular and clinical perspectives
AU - Rebelo, Rita
AU - Xavier, Cristina P. R.
AU - Giovannetti, Elisa
AU - Vasconcelos, M. Helena
N1 - Funding Information: This article is based upon work from the COST (European Cooperation in Science and Technology; https://www.cost.eu/) Actions IG17104–PANDORA and CA21116–TRANSPAN. The group of M.H.V. is supported in part by project NORTE-01-0145-FEDER-072678 – Consórcio PORTO.CCC – Porto.Comprehensive Cancer Center, and by project NORTE-01-0145-FEDER-000051, supported by Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). The group of E.G. is supported by the KWF Dutch Cancer Society (grant 11957) and Associazione Italiana per la Ricerca sul Cancro AIRC/IG (grant 24444). R.R. is supported by the Fundação para a Ciência e a Tecnologia (FCT) through PhD fellowship SFRH/BD/06622/2021. C.P.R.X. is supported by the FCT and the Fundo Social Europeu (FSE), Portugal, through postdoctoral grant SFRH/BPD/122871/2016. The authors declare no conflicts of interest. Funding Information: This article is based upon work from the COST (European Cooperation in Science and Technology; https://www.cost.eu/ ) Actions IG17104–PANDORA and CA21116–TRANSPAN. The group of M.H.V. is supported in part by project NORTE-01-0145-FEDER-072678 – Consórcio PORTO.CCC – Porto. Comprehensive Cancer Center , and by project NORTE-01-0145-FEDER-000051, supported by Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). The group of E.G. is supported by the KWF Dutch Cancer Society ( grant 11957 ) and Associazione Italiana per la Ricerca sul Cancro AIRC/IG ( grant 24444 ). R.R. is supported by the Fundação para a Ciência e a Tecnologia (FCT) through PhD fellowship SFRH/BD/06622/2021. C.P.R.X. is supported by the FCT and the Fundo Social Europeu (FSE), Portugal, through postdoctoral grant SFRH/BPD/122871/2016. Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/6
Y1 - 2023/6
N2 - Pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) are highly abundant cells in the pancreatic tumor microenvironment (TME) that modulate desmoplasia. The formation of a dense stroma leads to immunosuppression and therapy resistance that are major causes of treatment failure in pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that several subpopulations of CAFs in the TME can interconvert, explaining the dual roles (antitumorigenic and protumorigenic) of CAFs in PDAC and the contradictory results of CAF-targeted therapies in clinical trials. This highlights the need to clarify CAF heterogeneity and their interactions with PDAC cells. This review focuses on the communication between activated PSCs/CAFs and PDAC cells, as well as on the mechanisms underlying this crosstalk. CAF-focused therapies and emerging biomarkers are also outlined.
AB - Pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) are highly abundant cells in the pancreatic tumor microenvironment (TME) that modulate desmoplasia. The formation of a dense stroma leads to immunosuppression and therapy resistance that are major causes of treatment failure in pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that several subpopulations of CAFs in the TME can interconvert, explaining the dual roles (antitumorigenic and protumorigenic) of CAFs in PDAC and the contradictory results of CAF-targeted therapies in clinical trials. This highlights the need to clarify CAF heterogeneity and their interactions with PDAC cells. This review focuses on the communication between activated PSCs/CAFs and PDAC cells, as well as on the mechanisms underlying this crosstalk. CAF-focused therapies and emerging biomarkers are also outlined.
KW - biomarkers
KW - cancer-associated fibroblasts (CAFs)
KW - extracellular vesicles (EVs)
KW - intercellular communication
KW - pancreatic stellate cells (PSCs)
KW - therapeutic approaches
UR - http://www.scopus.com/inward/record.url?scp=85153404146&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.molmed.2023.03.002
DO - https://doi.org/10.1016/j.molmed.2023.03.002
M3 - Review article
C2 - 37100646
SN - 1471-4914
VL - 29
SP - 439
EP - 453
JO - Trends in molecular medicine
JF - Trends in molecular medicine
IS - 6
ER -