Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, USA; Department of Cancer Biology, University of Cincinnati, Cincinnati, OH, USA.
Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, USA.
Cancer Lett. 2024 Dec 1;606:217320. doi: 10.1016/j.canlet.2024.217320. Epub 2024 Nov 1.
The efficacy of radiation treatment (RT) of head and neck squamous cell carcinoma (HNSCC) is limited by radioresistance and the toxicity of FDA approved radiosensitizers. In extension to our previous research where we demonstrated that telaglenastat (CB839) increased efficacy of RT in in vitro and in vivo HNSCC models, here, we examine the radiosensitizing effects of telaglenastat in comparison to cisplatin's, as cisplatin is currently the standard of care for concurrent therapy. Combination of telaglenastat with RT reduced tumor volume in a HNSCC patient derived xenograft mouse model. The efficacy of telaglenastat with RT in reducing cell survival and increasing apoptosis was similar if not greater than that of cisplatin with RT in Cal27 and HN5 HNSCC cells. The addition of telaglenastat increased reactive oxygen species and reduced the antioxidant glutathione in both Cal27 and HN5 cells. Reverse Phase Protein Array analyses revealed alterations in cell death and DNA damage response proteins. This study provides the scientific underpinnings for the use of telaglenastat as a radiosensitizer in the treatment of HNSCC either as an alternative to cisplatin or in cisplatin-ineligible patients.
放射治疗（RT）对头颈部鳞状细胞癌（HNSCC）的疗效受到放射抗性和 FDA 批准的放射增敏剂的毒性的限制。在我们之前的研究中，我们证明了 telaglenastat（CB839）可提高体外和体内 HNSCC 模型中 RT 的疗效，在这里，我们将 telaglenastat 的放射增敏作用与顺铂进行比较，因为顺铂目前是同步治疗的标准治疗方法。telaglenastat 与 RT 的联合治疗可减少 HNSCC 患者来源异种移植小鼠模型中的肿瘤体积。在 Cal27 和 HN5 HNSCC 细胞中，telaglenastat 与 RT 的联合治疗在降低细胞存活率和增加细胞凋亡方面的疗效与顺铂与 RT 的联合治疗相似，如果不比顺铂与 RT 的联合治疗更好。telaglenastat 的添加增加了活性氧并减少了 Cal27 和 HN5 细胞中的抗氧化谷胱甘肽。反相蛋白阵列分析显示细胞死亡和 DNA 损伤反应蛋白发生改变。这项研究为 telaglenastat 作为放射增敏剂在 HNSCC 治疗中的应用提供了科学依据，无论是作为顺铂的替代品还是在不适合顺铂的患者中。
