TY - JOUR
T1 - Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma therapy
T2 - Challenges and opportunities
AU - Qin, Qin
AU - Yu, Rong
AU - Eriksson, John E.
AU - Tsai, Hsiang i.
AU - Zhu, Haitao
N1 - Publisher Copyright:
© 2024
PY - 2024/6/1
Y1 - 2024/6/1
N2 - Pancreatic ductal adenocarcinoma (PDAC) is a solid organ malignancy with a high mortality rate. Statistics indicate that its incidence has been increasing as well as the associated deaths. Most patients with PDAC show poor response to therapies making the clinical management of this cancer difficult. Stromal cells in the tumor microenvironment (TME) contribute to the development of resistance to therapy in PDAC cancer cells. Cancer-associated fibroblasts (CAFs), the most prevalent stromal cells in the TME, promote a desmoplastic response, produce extracellular matrix proteins and cytokines, and directly influence the biological behavior of cancer cells. These multifaceted effects make it difficult to eradicate tumor cells from the body. As a result, CAF-targeting synergistic therapeutic strategies have gained increasing attention in recent years. However, due to the substantial heterogeneity in CAF origin, definition, and function, as well as high plasticity, majority of the available CAF-targeting therapeutic approaches are not effective, and in some cases, they exacerbate disease progression. This review primarily elucidates on the effect of CAFs on therapeutic efficiency of various treatment modalities, including chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Strategies for CAF targeting therapies are also discussed.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a solid organ malignancy with a high mortality rate. Statistics indicate that its incidence has been increasing as well as the associated deaths. Most patients with PDAC show poor response to therapies making the clinical management of this cancer difficult. Stromal cells in the tumor microenvironment (TME) contribute to the development of resistance to therapy in PDAC cancer cells. Cancer-associated fibroblasts (CAFs), the most prevalent stromal cells in the TME, promote a desmoplastic response, produce extracellular matrix proteins and cytokines, and directly influence the biological behavior of cancer cells. These multifaceted effects make it difficult to eradicate tumor cells from the body. As a result, CAF-targeting synergistic therapeutic strategies have gained increasing attention in recent years. However, due to the substantial heterogeneity in CAF origin, definition, and function, as well as high plasticity, majority of the available CAF-targeting therapeutic approaches are not effective, and in some cases, they exacerbate disease progression. This review primarily elucidates on the effect of CAFs on therapeutic efficiency of various treatment modalities, including chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Strategies for CAF targeting therapies are also discussed.
KW - Cancer-associated fibroblasts
KW - Heterogeneity
KW - Pancreatic ductal adenocarcinoma
KW - Therapy resistance
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85190420602&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2024.216859
DO - 10.1016/j.canlet.2024.216859
M3 - Review Article or Literature Review
C2 - 38615928
AN - SCOPUS:85190420602
SN - 0304-3835
VL - 591
JO - Cancer Letters
JF - Cancer Letters
M1 - 216859
ER -