MET exon 14 skipping mutation is a hepatocyte growth factor (HGF)-dependent oncogenic driver in vitro and in humanised HGF knock-in mice.

Exon skipping mutations of the MET receptor tyrosine kinase (METex14), increasingly reported in cancers, occur in 3-4% of non-small-cell lung cancer (NSCLC). Only 50% of patients have a beneficial response to treatment with MET-tyrosine kinase inhibitors (TKIs), underlying the need to understand the mechanism of METex14 oncogenicity and sensitivity to TKIs. Whether METex14 is a driver mutation and whether it requires hepatocyte growth factor (HGF) for its oncogenicity in a range of in vitro functions and in vivo has not been fully elucidated from previous preclinical models.

c-Met-integrin cooperation: Mechanisms, tumorigenic effects, and therapeutic relevance.

c-Met is a receptor tyrosine kinase which upon activation by its ligand, the hepatocyte growth factor, mediates many important signalling pathways that regulate cellular functions such as survival, proliferation, and migration. Its oncogenic and tumorigenic signalling mechanisms, greatly contributing to cancer development and progression, are well documented. Integrins, heterogeneous adhesion receptors which facilitate cell-extracellular matrix interactions, are important in biomechanically sensitive cell adhesion and motility but also modulate diverse cell behaviour.

IL-10 in cancer: an essential thermostatic regulator between homeostatic immunity and inflammation - a comprehensive review.

Cytokines are soluble proteins that mediate intercellular signaling regulating immune and inflammatory responses. Cytokine modulation represents a promising cancer immunotherapy approach for immune-mediated tumor regression. However, redundancy in cytokine signaling and cytokines' pleiotropy, narrow therapeutic window, systemic toxicity, short half-life and limited efficacy represent outstanding challenges for cytokine-based cancer immunotherapies.