Research analysis on the mechanism of action and clinical targets of ceritinib/ceritinib (Zanda)

Ceritinib (Ceritinib, also known as ceritinib) is an oral second-generation ALK (anaplastic lymphoma kinase) inhibitor, mainly used to treat ALK positive non-small cell lung cancer (NSCLC) patients. The core of its mechanism of action is to specifically inhibit the activity of ALK tyrosine kinase, thereby blocking the signal transduction pathway of tumor cells and inhibiting the proliferation and survival of tumor cells. Compared with the first generation ALK inhibitors, ceritinib has stronger activity in inhibiting ALK resistance mutations, especially for The common L1196M and G1269A mutations can effectively overcome drug resistance and improve the sustained effect of clinical treatment.

In terms of target effects, ceritinib not only inhibits the ALK signaling pathway, but also has certain inhibitory effects on ROS1 and INSR/IGF1R and other related tyrosine kinases. By blocking the downstream signaling pathways such as PI3K/AKT, RAS/RAF/MEK/ERK and JAK/STAT, ceritinib can significantly reduce the proliferation rate of tumor cells and induce apoptosis. In addition, ceritinib also has a certain impact on angiogenesis in the tumor microenvironment. By reducing the expression of VEGF and other pro-vascular factors, it slows down the formation of tumor blood supply, thereby indirectly inhibiting tumor growth.

Clinical studies have shown that ceritinib has good efficacy in ALKpositive NSCLC patients. Multiple phase II and phase III clinical trials have shown that ceritinib has an overall response rate (ORR ) can reach 40%~50%, and the median progression-free survival (PFS) can reach 6~7 months. In addition, ceritinib also shows certain penetration and efficacy in patients with brain metastases, which can slow down the progression of central nervous system lesions and provide patients with more comprehensive treatment options.

In clinical application, the targeting properties of ceritinib make it the first or subsequent treatment drug for ALK positive patients. However, since drug resistance or adverse reactions may occur with long-term use, patients need to strictly follow medical instructions to take the medication and undergo regular imaging examinations and biomarker monitoring. Targeting the resistance mechanism, researchers are exploring strategies to combine other targeted drugs or immunotherapy to extend the duration of efficacy. Overall, ceritinib provides new clinical options and scientific basis for the treatment of lung cancer by precisely targeting ALK and its related signaling pathways.

Reference materials:https://www.drugs.com/