Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related morbidity and mortality in the western world, with limited therapeutic strategies and dismal long-term survival. Cancer-associated fibroblasts (CAFs) are key components of the pancreatic tumor microenvironment, maintaining the extracellular matrix, while also being involved in intricate crosstalk with cancer cells and infiltrating immunocytes. Therefore, they are potential targets for developing therapeutic strategies against PDAC. However, recent studies have demonstrated significant heterogeneity in CAFs with respect to their origins, spatial distribution, and functional phenotypes within the PDAC tumor microenvironment. Therefore, it is imperative to understand and delineate this heterogeneity prior to targeting CAFs for PDAC therapy.
Highlights
Both CD105+ and CD105− cancer-associated fibroblasts (CAFs) displayed expression of genes associated with previously described myofibroblastic CAFs” (myCAFs) and inflammatory CAFs” (iCAFs) subgroups, the apCAF expression profile seemed to be restricted to a subset of CD105− CAFs
The stromal compartment has undergone a great deal of investigation in the past decade, thanks to single-cell RNA-sequencing techniques, and as a result, we understand that CAFs are heterogenous entities, and this has changed the rationale of targeting CAFs in pancreatic ductal adenocarcinoma (PDAC) therapeutics
We are well aware that some CAFs can behave as protumorigenic, while others as antitumorigenic, and their targeting in solid malignancies demands their thorough characterization
Summary
Surgery remains the only curative option for potentially resectable patients, while patients with more advanced disease are usually treated with systemic therapies, such as chemotherapy [6,7]. The standard-of-care chemotherapy regimens do provide survival benefits, the overall survival still remains dismal. Aggressive biology and resistance to therapy are some of the factors that contribute to these poor outcomes [6]. Recent studies have demonstrated that, apart from the cancerous epithelial compartment, other cellular and non-cellular elements present in the tumor microenvironment (TME) of PDAC contribute substantially to its aggressive biology, progression, and metastasis [8,9]. PDAC TME has been extensively investigated as a target to modulate PDAC progression, and to enhance the efficacy of currently available anti-cancer therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
