TY - JOUR
T1 - The novel roles of stromal fibroblasts in metronomic chemotherapy: Focusing on cancer stemness and immunity
AU - Liao, Wen-Ying
AU - Chan, Tze-Sian
AU - Tsai, Kelvin K.
PY - 2017
Y1 - 2017
N2 - Metronomic chemotherapy involves the administration of cytotoxic chemotherapy at reduced doses administered at regular and frequent intervals. Low-dose metronomic (LDM) chemotherapy represents an alternative to standard maximum tolerated dose (MTD) chemotherapy as it is less toxic and offers additional beneficial biological effects; such effects include inhibition of tumor neovascularization and reduced recruitment of immune-suppressive cells. In desmoplastic cancers such as breast and pancreatic cancers, carcinoma-associated fibroblasts (CAFs) in the tumor stroma constitute an important cellular target of systemic chemotherapy, and the treatment-modulated CAFs may deleteriously influence treatment efficacy. Herein, we reviewed the novel roles of CAFs in metronomic chemotherapy in desmoplastic cancers. We discuss the differential effects of MTD- and LDM-chemotherapy on the heterotypic interactions among CAFs and cells in the other cancer compartments, emphasizing the roles of cancer stem cells and myeloid-derived suppressor cells. The novel mechanistic roles of CAFs in cancer therapy provide an additional rationale for the clinical development of LDM chemotherapy.
AB - Metronomic chemotherapy involves the administration of cytotoxic chemotherapy at reduced doses administered at regular and frequent intervals. Low-dose metronomic (LDM) chemotherapy represents an alternative to standard maximum tolerated dose (MTD) chemotherapy as it is less toxic and offers additional beneficial biological effects; such effects include inhibition of tumor neovascularization and reduced recruitment of immune-suppressive cells. In desmoplastic cancers such as breast and pancreatic cancers, carcinoma-associated fibroblasts (CAFs) in the tumor stroma constitute an important cellular target of systemic chemotherapy, and the treatment-modulated CAFs may deleteriously influence treatment efficacy. Herein, we reviewed the novel roles of CAFs in metronomic chemotherapy in desmoplastic cancers. We discuss the differential effects of MTD- and LDM-chemotherapy on the heterotypic interactions among CAFs and cells in the other cancer compartments, emphasizing the roles of cancer stem cells and myeloid-derived suppressor cells. The novel mechanistic roles of CAFs in cancer therapy provide an additional rationale for the clinical development of LDM chemotherapy.
KW - Carcinoma-associated fibroblasts
KW - Metronomic chemotherapy
KW - Cancer stemness
KW - Myeloid-derived suppressor cells
U2 - 10.1016/j.jcrpr.2017.08.001
DO - 10.1016/j.jcrpr.2017.08.001
M3 - Review article
SN - 2311-3006
VL - 4
SP - 123
EP - 126
JO - Journal of Cancer Research and Practice
JF - Journal of Cancer Research and Practice
IS - 4
ER -