Spleen tyrosine kinase (SYK): an emerging target for the assemblage of small molecule antitumor agents

Introduction: Spleen tyrosine kinase (SYK), a nonreceptor tyrosine kinase, has emerged as a vital component in the complex symphony of cancer cell survival and division. SYK activation (constitutive) is documented in various B-cell malignancies, and its inhibition induces programmed cell death. In some instances, it also acts as a tumor suppressor. Areas covered: Involvement of the SYK in the cancer growth, specifically in the progression of chronic lymphocytic leukemia (CLL), diffuse large B cell lymphomas (DLBCLs), acute myeloid leukemia (AML), and multiple myeloma (MM) is discussed. Therapeutic strategies to target SYK in cancer, including investigational SYK inhibitors, combinations of SYK inhibitors with other drugs targeting therapeutically relevant targets, and recent advancements in constructing new structural assemblages as SYK inhibitors, are also covered. Expert opinion: The SYK inhibitor field is currently marred by the poor translation rate of SYK inhibitors from preclinical to clinical studies. Also, dose-limited toxicities associated with the applications of SYK inhibitors have been evidenced. Thus, the development of new SYK inhibitory structural templates is in the need of the hour. To accomplish the aforementioned, interdisciplinary teams should incessantly invest efforts to expand the size of the armory of SYK inhibitors.