Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.
Journal
Nature reviews. Cancer
ISSN: 1474-1768
Titre abrégé: Nat Rev Cancer
Pays: England
ID NLM: 101124168
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
accepted:
09
02
2022
pubmed:
11
3
2022
medline:
1
6
2022
entrez:
10
3
2022
Statut:
ppublish
Résumé
Normal cells explore multiple states to survive stresses encountered during development and self-renewal as well as environmental stresses such as starvation, DNA damage, toxins or infection. Cancer cells co-opt normal stress mitigation pathways to survive stresses that accompany tumour initiation, progression, metastasis and immune evasion. Cancer therapies accentuate cancer cell stresses and invoke rapid non-genomic stress mitigation processes that maintain cell viability and thus represent key targetable resistance mechanisms. In this Review, we describe mechanisms by which tumour ecosystems, including cancer cells, immune cells and stroma, adapt to therapeutic stresses and describe three different approaches to exploit stress mitigation processes: (1) interdict stress mitigation to induce cell death; (2) increase stress to induce cellular catastrophe; and (3) exploit emergent vulnerabilities in cancer cells and cells of the tumour microenvironment. We review challenges associated with tumour heterogeneity, prioritizing actionable adaptive responses for optimal therapeutic outcomes, and development of an integrative framework to identify and target vulnerabilities that arise from adaptive responses and engagement of stress mitigation pathways. Finally, we discuss the need to monitor adaptive responses across multiple scales and translation of combination therapies designed to take advantage of adaptive responses and stress mitigation pathways to the clinic.
Identifiants
pubmed: 35264777
doi: 10.1038/s41568-022-00454-5
pii: 10.1038/s41568-022-00454-5
pmc: PMC9149051
mid: NIHMS1791096
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
323-339Subventions
Organisme : NCI NIH HHS
ID : R00 CA222554
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217842
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA253472
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA240243
Pays : United States
Informations de copyright
© 2022. Springer Nature Limited.
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