Centre for Cancer Research

Oncogenic signalling

Laboratory head: Associate Professor Terry Johns

Oncogenic signalling laboratory

The focus of the Oncogenic Signalling laboratroy is the identification and characterization of cellular networks that promote the survival and/or growth of cancer cells.  The team is particularly interested in receptors found on the cell surface that convert external messages to internal signals that promote uncontrolled cellular growth, a hallmark of cancer cells.  Once a receptor important to the cancer cells has been identified, we endeavor to develop antibodies that block the function of the receptor.  This specific form of treatment is known as targeted therapy.  Depending on the receptor targeted, blocking its function may induce growth arrest, cell death or sensitization to other agents such as chemotherapy.  This research has an emphasis on glioma (brain cancer) but also has implications for a wide variety of cancers including colon, breast, lung, and head & neck. 

Targeted therapies are considered by the research and clinical communities as the best option for the development of new therapeutics to treat cancer. However, this approach will only be effective if we understand how the different signalling pathways within individual tumour types, or sub-types, interact. The Oncogenic Signalling group is currently:

1. Developing novel antibodies that target signalling pathways (e.g. EGFR, c-met, IL-6, IL-13Ralpha2) critical to glioma growth and invasion
2. Determining how many signalling networks need to be targeted to achieve robust inhibition of a broad range of gliomas
3. Attempting to understand the signalling mediated by the EGFRvIII, a mutation of the EGFR commonly expressed in glioma
4.  P roviding new insights into cross-talk between signalling pathways relevant to glioma

Overall this work will lead to new therapeutic strategies for the treatment of glioma, a disease for which there is currently no effective treatment.

Key publications

Gan HK, Walker F, Burgess AW, Rigopoulos A, Scott AM, and Johns, TG (2007) The epidermal growth factor receptor (EGFR) tyrosine kiniase inhibitor AG1478 increases the formation of inactive untethered EGFR dimers: implications for combination therapy with monoclonal antibody 806, J Biol Chem, Vol 282, No 5, pp 2840-2850.

Johns, TG, Perera RM, Vernew SC, Vitali AA, Cao DX, Cavenee WK, Scott AM, Furnari FB (2007) The efficacy of epidermal growth factor receptor-specific antibodies against glioma xenografts is influenced by receptor levels, activation status, and heterodimerization. Clin Cancer Res, 2007 Mar 15;13(6):1911-25.

Perera, RM, Narita Y, Furnari FB, Gan HK, Murone C, Ahlkvist M, Luwor RB, Burgess AW, Stockert E, Jungbluth AA, Old LJ, Cavenee WK, Scott AM, Johns TG (2005) Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity. Clin Cancer Res. 2005 Sep 1;11(17):6390-9.

Johns TG, Adams TE, Cochran JR, Hall NE, Hoyne PA, Olsen MJ, Kim YS, Rothaker J, Nice EC, Walker F, Ritter G, Jungbluth AA, Ward CW, Burgess AW, Wittrup KD, Scott AM (2004), Identification of the epitope for the epidermal growth factor receptor-specific monoclonal antibody 806 reveals that it preferentially recognizes an untethered form of the receptor. J Biol Chem, 2004 Jul 16;279(29):30375-84.