Characterizing and Targeting of BCL-2 Family Members in Nasopharyngeal Carcinoma
- Author(s)
- Thai, AA; Young, RJ; Bressel, M; Kelly, GL; Sejic, N; Tsao, SW; Trigos, A; Rischin, D; Solomon, BJ;
- Journal Title
- Head & Neck
- Publication Type
- Online publication before print
- Abstract
- 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: 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: 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: Our study demonstrates the therapeutic potential of combining cisplatin and S63845, which warrants further investigation.
- Keywords
- Bcl2; BCLxl; Mcl1; Npc; apoptosis
- Department(s)
- Medical Oncology; Laboratory Research; Biostatistics and Clinical Trials
- Publisher's Version
- https://doi.org/10.1002/hed.27973
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-01-14 02:50:39
Last Modified: 2025-01-14 02:50:52