BCR-ABL and SRC family tyrosine kinases (BCR-ABL/SFK)

The BCR-ABL fusion protein and the SRC family of kinases (SFKs) represent a critical group of non-receptor tyrosine kinases involved in the pathogenesis of various hematologic and solid malignancies. BCR-ABL is a constitutively active kinase resulting from the Philadelphia chromosome translocation (t(9;22)), which drives the progression of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) [Source: PubMed PMID: 15592483]. The SRC family, including members such as SRC, LCK, and FYN, plays a pivotal role in regulating cell growth, survival, and cytoskeletal remodeling, and its dysregulation is often associated with tumor progression and resistance to therapy [Source: UniProt P12931]. Dasatinib is a potent, second-generation multi-kinase inhibitor that targets BCR-ABL and the SRC family, as well as other kinases like c-KIT, EPHA2, and PDGFRβ [Source: FDA Label for Sprycel]. By binding to the ATP-binding site of these kinases, dasatinib prevents the phosphorylation of downstream substrates, effectively inhibiting oncogenic signaling and inducing apoptosis in malignant cells [Source: StatPearls, Dasatinib]. This broad-spectrum activity allows for the treatment of patients who have developed resistance to first-generation inhibitors like imatinib, though it also contributes to a unique safety profile including pleural effusion and pulmonary arterial hypertension [Source: NIH, LiverTox].

Other names

BCR-ABL1 fusion proteinSRC family kinasesSFKsDasatinib-sensitive kinasesABL1SRCLCKYES1FYNc-KITPDGFRBEPHA2

ATP-competitive inhibition of the tyrosine kinase domain, preventing the phosphorylation of tyrosine residues on substrate proteins and blocking downstream oncogenic signaling pathways.