Non-receptor tyrosine kinase signaling pathways and therapeutic implications

Cell signaling regulates cellular physiological functions, including the cell cycle, survival, immune response, gene expression, and protein-protein interactions. Within this complex system and its intrinsic mechanisms, non-receptor tyrosine kinases (NRTKs) play a crucial role in signaling in the cellular cytoplasmic compartments. Owing to the involvement of NRTKs in the signaling cascade, they have made a significant contribution to the manifestation of etiologically complex diseases such as cancer, cardiovascular, neurodegenerative, autoimmune, and metabolic diseases, which are some of the major causes of mortality globally and often lack remedial measures. While understanding how NRTKs and their signaling pathways are involved in the onset of diseases is currently an emerging research topic, we noticed a lack of a broader picture of the commonalities between diseases and their corresponding pathologies. Thus, the goal of this review was to present a holistic view of NRTKs in cellular homeostasis, emphasizing both their convergent and divergent signaling roles within and across disease systems. Such approaches include shared pathways such as SRC/PI3K/AKT, JAK/STAT, MAPK, and FAK-integrin signaling that operate across disease systems, contributing to inflammation, immune modulation, metabolic reprogramming, and cellular stress responses. These common networks enable us to identify nodal points of convergence that are often co-opted or dysregulated across multiple pathologies. This review also demonstrates crosstalk concerning NRTKs' interactions with their cellular environment and other molecules with therapeutic potential. Additionally, current FDA-approved drugs and on-going clinical trials will provide a basis for understanding the effects of NRTKs-targeting drugs and their potential for application to other diseases, given their cascading mechanisms.