Characterizing and Targeting of BCL-2 Family Members in Nasopharyngeal Carcinoma.
BCL2
BCLxl
MCL1
NPC
apoptosis
Journal
Head & neck
ISSN: 1097-0347
Titre abrégé: Head Neck
Pays: United States
ID NLM: 8902541
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
revised:
26
08
2024
received:
03
04
2024
accepted:
12
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
aheadofprint
Résumé
The success of BH3 mimetics in hematological malignancies has spurred interest in their application in solid tumors. We examined the expression of the BCL-2 family of molecules in NPC tumors and cell lines and explored the anticancer efficacy of BH3 mimetics in vitro. Immunohistochemistry for BCL-2, MCL-1, BCL-xL, and transcriptomic analyses was conducted on NPC tumors. The efficacy of ABT-199, S63845, and ABT-737 were examined as monotherapy and in combination with cisplatin in NPC cell lines. RNA sequencing was performed to identify up and downregulated pathways in sensitive cell lines. One hundred and forty-nine EBV-positive NPC and 15 EBV-negative NPC were identified. Expression of BCL-2 was more frequent in EBV-positive NPC. BCL-2, MCL-1, and BCL-xL expression was not prognostic for overall survival. Marked sensitivity was seen with the combination of S63845 and cisplatin in NPC43. Our study demonstrates the therapeutic potential of combining cisplatin and S63845, which warrants further investigation.
Sections du résumé
BACKGROUND
BACKGROUND
The success of BH3 mimetics in hematological malignancies has spurred interest in their application in solid tumors. We examined the expression of the BCL-2 family of molecules in NPC tumors and cell lines and explored the anticancer efficacy of BH3 mimetics in vitro.
METHODS
METHODS
Immunohistochemistry for BCL-2, MCL-1, BCL-xL, and transcriptomic analyses was conducted on NPC tumors. The efficacy of ABT-199, S63845, and ABT-737 were examined as monotherapy and in combination with cisplatin in NPC cell lines. RNA sequencing was performed to identify up and downregulated pathways in sensitive cell lines.
RESULTS
RESULTS
One hundred and forty-nine EBV-positive NPC and 15 EBV-negative NPC were identified. Expression of BCL-2 was more frequent in EBV-positive NPC. BCL-2, MCL-1, and BCL-xL expression was not prognostic for overall survival. Marked sensitivity was seen with the combination of S63845 and cisplatin in NPC43.
CONCLUSION
CONCLUSIONS
Our study demonstrates the therapeutic potential of combining cisplatin and S63845, which warrants further investigation.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Research Grant Council, Hong Kong
ID : GRF-17122420
Organisme : Research Grant Council, Hong Kong
ID : GRF-17114818
Organisme : NSFC/RGC
ID : N_HKU735//18
Organisme : NSFC/RGC
ID : 81861168033
Informations de copyright
© 2024 Wiley Periodicals LLC.
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