Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update.
Antineoplastic Agents
/ therapeutic use
Epithelial-Mesenchymal Transition
/ drug effects
Humans
Immune System
/ drug effects
Molecular Targeted Therapy
/ methods
Neoplasm Recurrence, Local
Neoplasms
/ drug therapy
Neoplastic Stem Cells
/ drug effects
Signal Transduction
/ drug effects
Tumor Microenvironment
/ drug effects
Journal
Nature reviews. Clinical oncology
ISSN: 1759-4782
Titre abrégé: Nat Rev Clin Oncol
Pays: England
ID NLM: 101500077
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
accepted:
14
10
2019
pubmed:
4
12
2019
medline:
28
4
2020
entrez:
4
12
2019
Statut:
ppublish
Résumé
Cancer stem cells (CSCs) have important roles in tumour development, relapse and metastasis; the intrinsic self-renewal characteristics and tumorigenic properties of these cells provide them with unique capabilities to resist diverse forms of anticancer therapy, seed recurrent tumours, and disseminate to and colonize distant tissues. The findings of several studies indicate that CSCs originate from non-malignant stem or progenitor cells. Accordingly, inhibition of developmental signalling pathways that are crucial for stem and progenitor cell homeostasis and function, such as the Notch, WNT, Hedgehog and Hippo signalling cascades, continues to be pursued across multiple cancer types as a strategy for targeting the CSCs hypothesized to drive cancer progression - with some success in certain malignancies. In addition, with the renaissance of anticancer immunotherapy, a better understanding of the interplay between CSCs and the tumour immune microenvironment might be the key to unlocking a new era of oncological treatments associated with a reduced propensity for the development of resistance and with enhanced antimetastatic activity, thus ultimately resulting in improved patient outcomes. Herein, we provide an update on the progress to date in the clinical development of therapeutics targeting the Notch, WNT, Hedgehog and Hippo pathways. We also discuss the interactions between CSCs and the immune system, including the potential immunological effects of agents targeting CSC-associated developmental signalling pathways, and provide an overview of the emerging approaches to CSC-targeted immunotherapy.
Identifiants
pubmed: 31792354
doi: 10.1038/s41571-019-0293-2
pii: 10.1038/s41571-019-0293-2
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
204-232Subventions
Organisme : NCI NIH HHS
ID : R01 CA222571
Pays : United States
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