New insights into SYK targeting in solid tumors

• Published in: Trends in pharmacological sciences (Regular ed.) 2024-10, Vol.45 (10), p.904-918
• Main Author: Joshi, Shweta
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; B cells; Humans; macrophages; Molecular Targeted Therapy; myeloid cells; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - metabolism; Neoplasms - pathology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Signal Transduction; solid tumors; SYK; Syk Kinase - antagonists & inhibitors; Syk Kinase - metabolism; Tumor Microenvironment
• ISSN: 0165-6147; 1873-3735; 1873-3735
• DOI: 10.1016/j.tips.2024.08.006

Spleen tyrosine kinase (SYK), a non-receptor tyrosine kinase that is overexpressed in several solid tumors, presents a promising therapeutic target.SYK activation downstream of various receptors drives signaling pathways that facilitate tumor progression and immune evasion.SYK inhibition enhances the antitumor immune response in solid tumors by reprogramming myeloid and B cells or directly targeting tumor cells.SYK inhibition can overcome resistance to chemotherapy and immunotherapy in solid tumors.Clinical trials targeting SYK in solid tumors are underway. Spleen tyrosine kinase (SYK) is predominantly expressed in hematopoietic cells and has been extensively studied for its pivotal role in B cell malignancies and autoimmune diseases. In epithelial solid tumors, SYK shows a paradoxical role, acting as a tumor suppressor in some cancers while driving tumor growth in others. Recent preclinical studies have identified the role of SYK in the tumor microenvironment (TME), revealing that SYK signaling in immune cells, especially B cells, and myeloid cells, promote immunosuppression, tumor growth, and metastasis across various solid tumors. This review explores the emerging roles of SYK in solid tumors, the mechanisms of SYK activation, and findings from preclinical and clinical studies of SYK inhibitors as either standalone treatments or in combination with immunotherapy or chemotherapy for solid tumors. Spleen tyrosine kinase (SYK) is predominantly expressed in hematopoietic cells and has been extensively studied for its pivotal role in B cell malignancies and autoimmune diseases. In epithelial solid tumors, SYK shows a paradoxical role, acting as a tumor suppressor in some cancers while driving tumor growth in others. Recent preclinical studies have identified the role of SYK in the tumor microenvironment (TME), revealing that SYK signaling in immune cells, especially B cells, and myeloid cells, promote immunosuppression, tumor growth, and metastasis across various solid tumors. This review explores the emerging roles of SYK in solid tumors, the mechanisms of SYK activation, and findings from preclinical and clinical studies of SYK inhibitors as either standalone treatments or in combination with immunotherapy or chemotherapy for solid tumors.