<p>NVP-BSK805, an Inhibitor of JAK2 Kinase, Significantly Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma in vitro and in vivo</p>

Abstract

Purpose: Radiotherapy is one major curative treatment modality for esophageal squamous cell carcinoma (ESCC) patients. This study aimed to find out small-molecular kinase inhibitors, which can significantly enhance the radiosensitivity of ESCC in vitro and in vivo. Materials and Methods: Ninety-three kinase inhibitors were tested for their radiosensitizing effect in ESCC cells through high-content screening. The radiosensitizing effect of kinase inhibitors was investigated in vitro by detection of DNA double-strand breaks (DSBs) and clonogenic survival assay. By the establishment of xenograft tumor models in BALB/c nude mice, the radiosensitizing effect of kinase inhibitors was investigated in vivo. Results: Among the 93 kinase inhibitors tested, we found NVP-BSK805, an inhibitor of JAK2 kinase, significantly radiosensitized ESCC cells through enhancing DSBs, inhibiting DNA damage repair and arresting cell cycle in G2/M or G0/G1 phase. After treatment with NVP-BSK805, ESCC cells showed decreased clonogenic survival and delayed tumor growth in vivo. JAK2 kinase was highly expressed in tumor tissues of ESCC patients, while rarely expressed in matched normal esophageal epithelial tissues. Survival analysis revealed JAK2 kinase as a prognostic factor of ESCC patients treated with chemoradiotherapy. Conclusion: Our study discovered JAK2 kinase as an attractive target to enhance the radiosensitivity of ESCC cells in vitro and in vivo.

A novel immune-related radioresistant lncRNAs signature based model for risk stratification and prognosis prediction in esophageal squamous cell carcinoma

“…Radioresistance is the focus and difficulty in cancer radiobiology research, which is also a clinically urgent issue ( Wang et al, 2019 ; Yu et al, 2020 ; Sun et al, 2021 ; Liu et al, 2022 ). Genes are an intrinsic determinant of tumor radioresistance, and studies have shown that multiple genes can affect the radioresistance of esophageal cancer ( Huang et al, 2019 ; Wang et al, 2019 ; Hua et al, 2020 ; Yu et al, 2020 ; Han et al, 2021 ; Sun et al, 2021 ; Liu et al, 2022 ). Practice has shown that it is common in clinical practice that even patients with esophageal cancer of the same stage and the same pathological type have great differences in the effect of radiotherapy after receiving the same radiotherapy regimen.…”

“…Practice has shown that it is common in clinical practice that even patients with esophageal cancer of the same stage and the same pathological type have great differences in the effect of radiotherapy after receiving the same radiotherapy regimen. The fundamental reason is the genetic differences between different individuals ( Huang et al, 2019 ; Wang et al, 2019 ; Hua et al, 2020 ; Yu et al, 2020 ; Han et al, 2021 ; Sun et al, 2021 ; Liu et al, 2022 ). If the decisive genes of radioresistance can be screened out, it is of great significance for the study of radiosensitization, targeted therapy, and prediction of radiotherapy effect to guide individualized therapy.…”

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

“…The results demonstrated an attractive prospect of NVP-BSK805 in HNSCC. 355 CDK4/6 inhibitors The effect of CDK4/6 inhibitors is a hotpot in HNSCC. [356][357][358][359][360] Abemaciclib is the first CDK4/6 inhibitor that has been widely investigated.…”