<p>The Expression and Therapeutic Potential of Checkpoint Kinase 2 in Laryngeal Squamous Cell Carcinoma</p>

Abstract

Introduction: Laryngeal squamous cell carcinoma (LSCC) is the most common histological subtype of laryngeal cancer. The involved molecular mechanisms and suitable therapeutic targets for LSCC still need to be further investigated. Checkpoint kinase 2 (CHK2) participates in several cellular physiology pathways and plays a role in tumor progression. However, the roles of CHK2 in LSCC remain unclear. Methods: mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) database, and bioinformatic analysis was performed. Western blot and immunohistochemical analyses were conducted to detect protein expression. MTS assays were performed to examine cell growth of LSCC-derived cell lines. Results: In the present study, we found that both active form of CHK2 and total CHK2 protein expressions were up-regulated in LSCC tissues. Positive expression of CHK2 was closely associated with advanced clinical features and poor prognosis. Moreover, potential CHK2-involving bioprocesses and signaling pathways were analyzed. In addition, repressed proliferation of LSCC cells was induced by CHK2 inhibitor. Discussion: Taken together, our findings elucidated that CHK2 may act as an oncogenic factor in LSCC, suggesting a potential target for clinical treatment.

Could Inhibiting the DNA Damage Repair Checkpoint Rescue Immune-Checkpoint-Inhibitor-Resistant Endometrial Cancer?

“…However, a phase I dose-escalation study reported that AZD7762 + gemcitabine yielded limited efficacy in patients with metastatic or unresectable advanced solid tumors, and the risk of adverse cardiotoxicity outweighed the treatment benefit, resulting in research discontinuation [64], which suggests that more clinical trials are needed to determine whether AZD7762 can be applied for the treatment of human tumors. BML-277 (a CHK2 inhibitor) was reported to inhibit the growth of laryngeal squamous cell cancer cells [65]. Likewise, Hseih et al [66] found that BML-277 successfully inhibited the growth of oxaliplatin-resistant CRC cells in vitro and in vivo tumor models.…”