TY - JOUR
T1 - Targeting cancer stem cells
T2 - A strategy for effective eradication of cancer
AU - Shibata, Masahiro
AU - Hoque, Mohammad Obaidul
N1 - Funding Information:
This work was funded by NCI R01CA206027 R and NCI 01CA208709 (to M.O.H.).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/5
Y1 - 2019/5
N2 - Cancer stem cells (CSCs) are subpopulations of tumor cells with the ability to self-renew, differentiate, and initiate and maintain tumor growth, and they are considered to be the main drivers of intra-and inter-tumoral heterogeneity. While conventional chemotherapy can eradicate the majority of non-CSC tumor cells, CSCs are often drug-resistant, leading to tumor recurrence and metastasis. The heterogeneity of CSCs is the main challenge in developing CSC-targeting therapy; therefore, we and other investigators have focused on developing novel therapeutic strategies that combine conventional chemotherapy with inhibitors of CSC-regulating pathways. Encouraging preclinical findings have suggested that CSC pathway blockade can indeed enhance cellular sensitivity to non-targeted conventional therapy, and this work has led to several ongoing clinical trials of CSC pathway inhibitors. Our studies in bladder cancer and lung adenocarcinoma have demonstrated a crucial role of YAP1, a transcriptional regulator of genes that promote cell survival and proliferation, in regulating CSC phenotypes. Moreover, using cell lines and patient-derived xenograft models, we showed that inhibition of YAP1 enhances the efficacy of conventional therapies by attenuating CSC stemness features. In this review, we summarize the therapeutic strategies for targeting CSCs in several cancers and discuss the potential and challenges of the approach.
AB - Cancer stem cells (CSCs) are subpopulations of tumor cells with the ability to self-renew, differentiate, and initiate and maintain tumor growth, and they are considered to be the main drivers of intra-and inter-tumoral heterogeneity. While conventional chemotherapy can eradicate the majority of non-CSC tumor cells, CSCs are often drug-resistant, leading to tumor recurrence and metastasis. The heterogeneity of CSCs is the main challenge in developing CSC-targeting therapy; therefore, we and other investigators have focused on developing novel therapeutic strategies that combine conventional chemotherapy with inhibitors of CSC-regulating pathways. Encouraging preclinical findings have suggested that CSC pathway blockade can indeed enhance cellular sensitivity to non-targeted conventional therapy, and this work has led to several ongoing clinical trials of CSC pathway inhibitors. Our studies in bladder cancer and lung adenocarcinoma have demonstrated a crucial role of YAP1, a transcriptional regulator of genes that promote cell survival and proliferation, in regulating CSC phenotypes. Moreover, using cell lines and patient-derived xenograft models, we showed that inhibition of YAP1 enhances the efficacy of conventional therapies by attenuating CSC stemness features. In this review, we summarize the therapeutic strategies for targeting CSCs in several cancers and discuss the potential and challenges of the approach.
KW - Cancer
KW - Cancer stem cell
KW - Combinational therapy
KW - Verteporfin
KW - YAP1
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U2 - 10.3390/cancers11050732
DO - 10.3390/cancers11050732
M3 - Review article
C2 - 31137841
AN - SCOPUS:85067410793
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 5
M1 - 732
ER -