Our research team is focused on translating laboratory research into clinical action for our patients with cancer.
Gaining an understanding of the process of transcription has highlighted opportunities to target cancer initiation, metastatic spread and therapy optimisation. We are currently engaged in four clinical trials that range from cancer vaccines, surgery optimisation and ameliorating inflammatory events that exacerbate metastatic spread.
Colorectal and breast cancer therapies
Industry and funding agencies (along with patients) have invested an extraordinary amount of money and effort into targeted cancer therapies. On average, the cost of registration by the FDA of a new therapy is USD$1.2-$1.8 billion, with the median improved progression-free survival (PFS) and overall survival (OS) being 2.4 and 2.1 months, respectively, for the 72 agents listed since 2002. These data are essentially the same for the seven therapies specifically listed for colorectal cancer and the nine therapies designated for breast cancer, showing a slightly better improvement (PFS of 3.0 months and OS of 2.7 months).
Colorectal cancer and breast cancer are the major tumour types of research activity in our group. However, we are also investigating other lower gastrointestinal (GI) cancers, specifically anal and rectal, as well as liver metastases from these anatomical sites.
New strategies are urgently required if we are to achieve an advance in meaningful and enduring increased survival of our patients (colorectal and breast cancer). To do this, informed by the consistent participation in the lower GI multidisciplinary team (MDT) meetings at Peter Mac, we are exploring three innovative approaches.
First is to proactively employ the cancer patient’s immune system to optimise their immunological response to their tumours, using peptide and DNA vaccine strategies.
Second is to directly target essential transcriptional processes rather than upstream signalling pathways, thereby avoiding the recurring therapy resistance via signalling pathway bypass.
Third is to optimise cancer surgery to reduce metastatic spread and improve patient recovery.
These projects are being conducted in collaboration with established clinician researchers with international standing and by training and mentoring new ones, along with the support of international commercial partners (TARGOVAX, USA, and Fisher and Paykel Health Care, NZ) and funding partners (Victorian Cancer Agency and the Adenoid Cystic Carcinoma Foundation, USA).
Gonda TJ, Ramsay RG (2015). Directly targeting transcriptional dysregulation in cancer. Nat Rev Cancer.15(11):686-694.
Cross RS, Malaterre J, Davenport AJ, Carpinteri S, Anderson RL, Darcy PK, Ramsay RG (2015). Therapeutic DNA vaccination against colorectal cancer by targeting the MYB oncoprotein. Clin Transl Immunology.4:e30.
Carpinteri S, Sampurno S, Bernardi MP, Germann M, Malaterre J, Heriot A, Chambers BA, Mutsaers SE, Lynch AC, Ramsay RG (2015). Peritoneal Tumorigenesis and Inflammation are Ameliorated by Humidified-Warm Carbon Dioxide Insufflation in the Mouse. Ann Surg Oncol.22(Suppl 3):1540-1547.
Xu H, Yan Y, Deb S, Rangasamy D, Germann M, Malaterre J, Eder NC, Ward RL, Hawkins NJ, Tothill RW, Chen L, Mortensen NJ, Fox SB, McKay MJ, Ramsay RG (2014). Cohesin Rad21 Mediates LOH and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors. Cell Rep.9:1781-1797.
Germann M, Xu H, Malaterre J, Sampurno S, Huyghe M, Cheasley D, Fre S, Ramsay RG (2014). Tripartite interactions between Wnt signaling, Notch and Myb for stem/progenitor cell functions during intestinal tumorigenesis. Stem Cell Res.13(3 Pt A):355-66.
Ramsay RG, Gonda TJ (2008). MYB function in normal and cancer cells. Nat Rev Cancer.8:523-534.