Abstract:
The Her receptor tyrosine kinase family has four members, namely Her-1 (EGFR or ErB1), Her-2 (Neu or ErbB2), Her-3 (ErB3) and Her-4 (ErB4). Activation of the kinases results in intracellular signalling events leading to some oncogenic and aggressive behaviour of cancer cells including those involved in cell growth, apoptosis and cellular migration and invasiveness. Known downstream signalling events include activation of the Ras, PI3K, MAPK pathways. Clinically, the levels of the Her family members have been shown to be aberrantly expressed in various tumour types including breast cancer and lung cancer. Mutations of the coding genes for the family members have also been found in solid cancers and have been key indicators for the choice and success of anti-Her treatments. Our team has been investigating the relationship between the Her family gene expression levels and the clinical outcomes of patients with breast, gastric, pancreatic and lung cancers and exploring the prospects and potential mechanisms of targeting Her kinases in the intervention of metastatic diseases from these cancers in particular in their bone and brain metastases. Significant correlations were found between the expression levels of selective members of the Her family and the overall as well as disease free survivals in these cancer types. Using cancer cell models, brain endothelial cell models and in vitro ‘metastasis’ models, combined with protein kinase platform technologies, we further explored the prospect of specific and broad spectrum inhibitors to the Her kinases on the invasive and metastatic behaviour of cancer cells. We have identified that certain broad spectrum Her kinase inhibitors, for example Nerlynx, have some profound effects on the bone and brain metastatic properties of cancer cells and also impact on the permeability of brain endothelial cells. Together with the clinical cohort results, our protein kinase platform assays have also identified patterns of responsive signalling events that may contribute to the anti-metastatic properties of the Her kinase inhibitors. In summary, our studies on the expression of the Her family kinases in clinical cancer cohorts together with laboratory investigation have shown that targeting certain Her family kinases are highly useful when treating metastatic cancers including those metastasised to bone and brain. We have also identified patterns of responsive signalling events that may allow prediction of the likelihood in patient’s response to the anti-Her treatment.
Biography:
Professor Wen G. Jiang is a Professor of Surgery and Tumour Biology at Cardiff Medical School of Cardiff University. He is currently the Director of Cardiff’s China Medical Research Collaborative (CCMRC) and Cardiff University Dean of International. Professor Jiang’s research interest is the molecular and cellular basis of cancer invasion and metastasis and development of anti-metastasis treatment.
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