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Introduction: Platinum-based chemotherapy remains the standard treatment for patients with SCLC, but the benefit of the treatment is often hampered by rapid development of drug resistance. Thus far, there is no targeted therapy available for SCLC. More than 90% of SCLC tumors harbor mutations in the tumor suppressor gene tumor protein p53 (p53), an important DNA damage checkpoint regulator, and these tumor cells rely predominantly on the checkpoint kinases to control DNA damage response.Methods: We examined whether and how inhibition of checkpoint kinase 1 (Chk1) affects cisplatin cytotoxicity in SCLC cells with and without p53 mutations, and evaluated the effect of Chk1 inhibitor and cisplatin combination in cisplatinsensitive and -resistant preclinical models.Results: Inhibition of Chk1 synergized with cisplatin to induce mitotic cell death in the p53-deficeint SCLC cells. The effect was regulated in part through activation of caspase 2 and downregulation of E2F transcription factor 1 (E2F1). Furthermore, Chk1 inhibitors prexasertib and AZD7762 enhanced cisplatin antitumor activity and overcame cisplatin resistance in SCLC preclinical models in vitro an in vivo. We also observed that higher expression of Chk1 was associated with poorer overall survival of patients with SCLC.Conclusions: Our data account Chk1 as a potential therapeutic target in SCLC, and rationalize clinical development of Chk1 inhibitor and cisplatin combinational strategy for the treatment of SCLC.

Background: SDH5 is in tumors. However, the functional role of SDH5 in lung cancer remains unknown. Results: SDH5 expression regulates EMT. Conclusion: SDH5 functions as a critical protein in the regulation of EMT by modulating the GSK-3␤-␤-catenin signaling pathway. Significance: SDH5 may be a prognostic biomarker and potential therapeutic target for lung cancer metastasis.

Background To assess the potential prognostic value of the albumin to alkaline phosphatase ratio (AAPR) in patients with non‐small cell lung cancer (NSCLC) after surgery. Methods The log‐rank and Kaplan‐Meier analyses were performed to detect differences in survival levels between different groups. A model of Cox proportional hazards was used to perform univariate and multivariate survival analyses. Comparisons of receiver operating characteristic (ROC) curves and the likelihood ratio test (LRT) were also utilized to compare the prognostic abilities of different systems for overall survival (OS) prediction. Results The optimal cut‐off value of the preoperative AAPR was 0.64. A decreased AAPR was associated with several clinicopathological and clinicolaboratory variables related to cancer progression. The preoperative AAPR of patients was positively correlated with the poor prognosis of NSCLC. In multivariate analyses, the preoperative AAPR was identified as an independent prognostic factor for disease‐free survival (DFS; P = 0.001) and overall survival (OS; P = 0.003). The LRT showed that the AAPR tumor‐node‐metastasis (TNM) system presented a significantly larger χ2 value (112.4 vs. 89.2, respectively, P < 0.01) and a relatively smaller Akaike information criterion (AIC) value (2955 vs. 2977, respectively, P < 0.01) than the TNM staging system. Conclusion Preoperative AAPR was a potentially valuable prognostic factor in NSCLC patients who underwent surgery. Our results further showed that the AAPR‐TNM system was superior to the current TNM staging system.

Our data showed that the combination of everolimus and gefitinib exhibits dose-dependent synergism in primary and acquired gefitinib-resistant NSCLC cells. Thus, a preclinical rationale exists for the use of everolimus to enhance the efficacy of gefitinib in EGFR-TKI-resistant patients with NSCLC.