The literature provides compelling evidence for the role of MET signaling in cancer development

and progression. The finding that cancer cells 那个 often use MET activation to escape therapies targeting other pathways strengthens the argument for MET-targeted therapeutics. Diverse strategies have been explored to deactivate MET signaling, and compounds and biologics targeting the MET pathway are in clinical development. Despite promising results from various clinical trials, we are still waiting for true MET-targeted therapeutics in the clinic. This review will explore recent progress and hurdles in the pursuit of METtargeted cancer drugs and discuss the challenges in such development.
肺腺癌是最常见的非小细胞肺癌组织学类型。目前,针对肺腺癌的分子靶向治疗是研究热点。继EGFR、KRAS、ALK等熟知驱动基因之后,不断有新的靶点基因被发现。本文重点就ROS1融合基因型肺癌的分子病理学、临床特点、检测手段及其治疗和预后的意义进行综述。
Objective This study investigated the role of the STAT3/survivin signaling pathway in the EML4-ALK–positive lung adenocarcinoma cell line H2228 before and after crizotinib-induced resistance. The mechanism of resistance was studied. Methods Cell viability

was determined using the MTT assay. Dactolisib Crizotinib-induced apoptosis in H2228 and H2228 crizotinib-resistant cells treated with the indicated doses of crizotinib was measured at different times(24 h, 48 h, 72 h) using flow cytometry. The levels of p-ALK, ALK, p-STAT3, STAT3, and survivin after treatment of cells

with 0, 0.3, and 1 μM crizotinib for 72 h were determined using Western blot analysis. DNA sequencing was used to identify mutations in H2228 crizotinib-resistant cells. Results The crizotinib IC50 values in H2228 and H2228 crizotinib-resistant cells at 72 h were 334.5 n M and 3418 n M, respectively. The resistance index of H2228 crizotinib-resistant cells was 10.20. Crizotinib induced apoptosis in H2228 cells and reduced the levels of p-ALK, p-STAT3, and survivin. In contrast, no changes in the levels of p-ALK, p-STAT3, and survivin were observed in H2228 crizotinib-resistant cells. The mutations 2067G→A 点击此处 and 2182G→C in EML4-ALK were present in the H2228 crizotinib-resistant cells. Conclusion Crizotinib decreased the viability of H2228 cells in a dose- and time-dependent manner. In the STAT3/survivin pathway, downregulation of p-ALK, p-STAT3, and survivin might contribute to crizotinib-induced apoptosis in H2228 cells. However, the STAT3/survivin pathway in H2228 crizotinib-resistant cells was unaffected by crizotinib treatment. Acquired resistance in H2228 cells might be related to ALK mutations.