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MET (hepatocyte growth factor receptor) and RON (recepteur dorigine Nantaise) are members of the MET proto-oncogene family of receptor tyrosine kinases (RTKs). Signalling from MET or RON activates multiple signalling pathways and ultimately promotes tumorigenesis and the formation of metastases. Mutations in MET have been detected in abundance in squamous cell carcinoma of the head and neck (SCCHN) metastases relative to the primary tumour, suggesting that this is a critical oncogene regulating dissemination. The biological significance of RON in SCCHN is still relatively unexplored. As survival has plateaued for patients with SCCHN, novel therapies with effects on the primary tumour and metastatic disease are urgently required. Small molecule inhibition of MET has been achieved in the pre-clinical setting and future clinical development is an exciting prospect. In this review, we summarise the biology of MET and RON RTKs and their contribution to an invasive tumour phenotype. We highlight their potential as therapeutic targets and address putative roles for MET and RON in resistance to conventional therapy, with particular reference to SCCHN.

Squamous cell carcinoma of the head and neck (SCCHN) is associated with high morbidity and mortality. Despite significant surgical advances and refinement in the delivery of chemotherapy and radiotherapy, prognosis has improved little in recent decades. Better local control has led to the late presentation of distant metastases and novel therapeutic agents are urgently required to prevent relapse, control disseminated disease and thus improve survival. PIK3CA encodes the p110α isoform of phosphoinositide 3-kinase (PI3-K) and is important in SCCHN, aberrations in its activity occurring early in the oncogenic process. PI3-K signalling promotes cell survival, proliferation, invasion and angiogenesis, all contributing to tumour progression. Activation of the PI3-K pathway may also mediate resistance to chemotherapy, radiotherapy and novel therapeutic agents such as epidermal growth factor receptor inhibitors. Elements of this signalling matrix, therefore, offer attractive therapeutic targets in SCCHN as inhibition of many malignant characteristics, as well as sensitisation to multiple treatment modalities, could be anticipated.