Study on the association between bosutinib/bosutinib and Src kinase inhibition

Bosutinib is a broad-spectrum tyrosine kinase inhibitor (TKI) originally developed to treat chronic myeloid leukemia (CML), especially for patients who are resistant to first-generation TKIs such as imatinib. Unlike other TKIs, bosutinib not only potently inhibits the activity of BCR-ABL fusion proteins, but also has a significant inhibitory effect on Src family kinases (SFKs). This mechanism makes its role in tumor treatment constantly re-examined.

Src family kinases include Src, Lyn, Fyn, Yes and other proteins. They are important regulators involved in cell signaling. They are widely distributed in a variety of tissue cells and are especially closely related to cell proliferation, migration, differentiation and survival. Src kinase is found to be overexpressed or continuously activated in the occurrence and development of various malignant tumors, and is common in breast cancer, lung cancer, pancreatic cancer and even some leukemias. Studies have found that Src kinase can cooperate with the signal transduction pathway of BCR-ABL kinase to accelerate malignant transformation of cells and the formation of drug resistance. Bosutinib is based on this multi-mechanical intervention pathway, which can block the pathological signaling network of BCR-ABL and Src kinase at the same time, thereby enhancing the therapeutic effect, especially showing a broader spectrum of activity in CML facing drug-resistant mutations or high-risk progression.

Compared with otherTKIs such as dasatinib and nilotinib, bosutinib shows unique advantages in inhibiting Src family kinases. Its target selectivity reduces the inhibition of non-target kinases such as KIT and PDGFR, thereby reducing potential toxic side effects and improving patient drug tolerance. It is worth mentioning that some basic research is evaluating the impact of bosutinib on the Src-mediated survival mechanism of cancer stem cells, which will provide a theoretical basis for its future extended application in hematological malignancies and certain solid tumors.

Reference materials:https://go.drugbank.com/drugs/DB06616