NCI-H2228 Brigatinib Drug Resistance Cell
Item | Cat# | Price |
Drug Resistance Cell | SNB-DR-0022 | Inquiry |
Compound Test Services | CT-002 | Inquiry |
Product Description
Brigatinib is an oral, potent, and selective ALK inhibitor indicated for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC) who have experienced disease progression or intolerance following crizotinib therapy.
Screeningbio‘s NCI-H2228/Brigatinib resistance cell line generated by exposing to increasing concentration of drug for certain period of time. After stable acquire resistance, cells were harvested and characterized for drug resistance by 7 days proliferation assay.
Data
Target Background
Brigatinib (Alunbrig) is a next‑generation anaplastic lymphoma kinase (ALK) inhibitor that targets ALK fusion proteins and multiple resistant ALK mutants. It suppresses ALK phosphorylation and downstream signaling pathways, including PI3K/Akt, MAPK, and JAK/STAT, leading to cell cycle arrest and apoptosis in ALK‑positive non‑small cell lung cancer (NSCLC) and other ALK‑driven malignancies. However, the development of drug resistance remains a major challenge limiting its long‑term efficacy.
Mechanistically, brigatinib resistance arises through multiple cellular adaptations. Secondary mutations in the ALK kinase domain (e.g., G1202R, L1196M, E1210K, and others that reduce drug binding affinity) are a common on‑target mechanism. Upregulation of efflux transporters such as P‑glycoprotein (MDR1/ABCB1) decreases intracellular drug accumulation, while activation of bypass signaling pathways—including EGFR, SRC, IGF‑1R, and MET—promotes survival independently of ALK. Additionally, activation of epithelial–mesenchymal transition (EMT), enhanced autophagy, or amplification of the ALK fusion gene also contribute to reduced drug sensitivity.
Understanding these mechanisms is critical for designing strategies to overcome resistance, such as developing fourth‑generation ALK inhibitors targeting resistant mutations, combining brigatinib with SRC or MET inhibitors, using efflux transporter modulators, or employing patient‑derived resistant cell models to guide personalized therapy development.