STAT3 inhibition suppresses adaptive survival of ALK-rearranged lung cancer cells through transcriptional modulation of apoptosis.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
28 Feb 2022
28 Feb 2022
Historique:
received:
18
06
2021
accepted:
03
02
2022
entrez:
1
3
2022
pubmed:
2
3
2022
medline:
2
3
2022
Statut:
epublish
Résumé
Patients with advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer who are prescribed ALK-tyrosine kinase inhibitors (ALK-TKIs) rarely have complete responses, with residual tumors relapsing as heterogeneous resistant phenotypes. Herein, we investigated new therapeutic strategies to reduce and eliminate residual tumors in the early treatment phase. Functional genomic screening using small guide RNA libraries showed that treatment-induced adaptive survival of ALK-rearranged lung cancer cells was predominantly dependent on STAT3 activity upon ALK inhibition. STAT3 inhibition effectively suppressed the adaptive survival of ALK-rearranged lung cancer cells by enhancing ALK inhibition-induced apoptosis. The combined effects were characterized by treatment-induced STAT3 dependence and transcriptional regulation of anti-apoptotic factor BCL-X
Identifiants
pubmed: 35228642
doi: 10.1038/s41698-022-00254-y
pii: 10.1038/s41698-022-00254-y
pmc: PMC8885877
doi:
Types de publication
Journal Article
Langues
eng
Pagination
11Subventions
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 20K08516
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 19K16738
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 19H03665
Informations de copyright
© 2022. The Author(s).
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