LYN proto-oncogene, Src family tyrosine kinase (LYN) and Bruton's tyrosine kinase (BTK) (LYN/BTK)

LYN (Lck/Yes-related novel protein tyrosine kinase) and BTK (Bruton's tyrosine kinase) are non-receptor tyrosine kinases that serve as critical mediators in the B-cell receptor (BCR) signaling pathway [3, 20]. BTK is a member of the Tec family and is indispensable for B-cell maturation, survival, and activation [6, 10]. LYN, a Src family kinase, functions as a signaling rheostat that can both initiate activation and mediate inhibitory feedback within B cells [7, 20]. In B-cell malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), these kinases are often overactive, driving tumor growth and survival [1, 4]. While BTK inhibitors like ibrutinib have revolutionized treatment, resistance frequently develops through BTK mutations or the activation of bypass pathways involving LYN [9, 18]. Dual inhibition of LYN and BTK is designed to provide a more comprehensive blockade of BCR signaling, effectively targeting both BTK-dependent and BTK-independent resistance mechanisms [2, 11]. Investigational agents such as birelentinib (DZD8586) and luxeptinib (CG-806) are currently being evaluated for their ability to treat relapsed or refractory B-cell cancers [5, 13].

Other names

Lck/Yes-related novel protein tyrosine kinasep56Lynp53LynJTK8Bruton agammaglobulinemia tyrosine kinaseAGMX1ATKBPKIMD1PSCTK1XLA

Dual inhibition of BTK and LYN to block both BTK-dependent and BTK-independent B-cell receptor signaling pathways, thereby overcoming resistance to single-target kinase inhibitors.