Gastrointestinal stromal tumor 430 cell line (GIST430)

GIST430 is a human gastrointestinal stromal tumor (GIST) cell line that serves as a critical model for studying imatinib resistance in cancer research [1, 2]. It was established from a patient whose tumor progressed during imatinib therapy and is characterized by a primary KIT exon 11 deletion (V560_L576del) and a secondary KIT exon 13 missense mutation (V654A) [2, 9]. The secondary V654A mutation occurs in the ATP-binding pocket of the KIT receptor tyrosine kinase, significantly reducing the binding affinity of imatinib and leading to therapeutic failure [5, 6]. While resistant to imatinib, GIST430 cells remain sensitive to second-line agents like sunitinib, which can effectively inhibit the V654A mutant protein [1, 9]. This cell line is also used to investigate alternative survival mechanisms, such as the activation of the insulin receptor (IR) pathway via IGF2 overexpression, which can provide bypass signaling in the presence of KIT inhibition [1, 13]. Consequently, GIST430 is an essential tool for the development and testing of next-generation tyrosine kinase inhibitors and combination therapies designed to overcome heterogeneous resistance in advanced GIST [10, 14].

Other names

GIST-430GIST 430

Inhibition of KIT receptor tyrosine kinase and insulin receptor (IR) signaling