Tyrosine-protein kinase Yes (c-Yes) (c-Yes)

Tyrosine-protein kinase Yes (c-Yes) is a non-receptor tyrosine kinase and a prominent member of the Src family of kinases (SFK) [1, 5]. It functions as a critical signaling hub, relaying messages from various cell surface receptors to downstream pathways such as PI3K/AKT, RAS/MAPK, and the Hippo/YAP1 axis to regulate cell growth, survival, and motility [1, 2, 7]. In many human malignancies, including lung, breast, and esophageal cancers, the YES1 gene is frequently amplified or overexpressed, driving tumor progression and metastatic spread [1, 5, 8]. Beyond its role as a primary oncogene, c-Yes is a significant factor in therapeutic resistance, particularly against EGFR and HER2 inhibitors, where it provides compensatory survival signaling [1, 2, 8]. While multi-kinase inhibitors like dasatinib target c-Yes, their use in solid tumors is often hampered by systemic toxicities, prompting the development of highly selective YES1 inhibitors [1, 5, 7]. These next-generation agents aim to provide more precise therapeutic options for patients whose tumors exhibit YES1-driven pathology or resistance [2, 7].

Other names

YES1Proto-oncogene c-Yesp61-YesYamaguchi sarcoma viral oncogene homolog 1

ATP-competitive inhibition of the kinase domain, leading to the suppression of downstream oncogenic signaling pathways such as PI3K/AKT, RAS/MAPK, and Hippo/YAP1 [2, 7].