The Translational Research Laboratory fosters collaboration between the laboratory research and clinical areas of Peter Mac.
We do this through investigating the application of new targeted cancer therapies by integrating cell biology, molecular biology, functional imaging and clinical trials.
The Biomarkers team focuses on identifying predictive and prognostic biomarkers in lung cancer, head and neck cancer and melanoma. The research team performs research to identify robust biomarkers that predict response to therapy, correlating these with disease outcome in patients. This major focus on new biomarkers to predict treatment response will enable better selection of patients for appropriate therapies. Using human tissue samples sourced from clinical trials and archives, researchers focus on identifying and then validating biomarkers in lung cancer, head and neck cancer and melanoma, using a range of techniques, including immunohistochemistry, in situ hybridisation, ELISA and PCR.
Specific projects include:
- Investigating prognostic and predictive biomarkers of hypoxia in head and neck squamous cell cancer.
- Investigating biomarkers of human papilloma virus infection in tonsil cancer and their relationship to patient outcomes.
- Investigating circulating tumour cells and circulating tumour DNA as prognostic and predictive biomarkers in melanoma, and to track longitudinal genomic changes during treatment.
The Developmental Therapeutics team performs pre-clinical evaluation of novel compounds for activity as anti-cancer drugs. The team, led by Dr Carleen Cullinane, interacts with academia and the biotechnology and pharmaceutical sectors in utilising a wide range of in vitro and in vivo assays to evaluate novel compounds for anti-tumour activity. In vitro assessments include cell proliferation and clonogenic survival assays; in vivo assays include dose finding studies, human tumour xenografts, syngeneic models, and single agent or combination studies with chemotherapy, immunotherapy or radiation therapy.
The basis of tumour response is also evaluated using tissue biomarker analyses. Non-invasive PET imaging is performed in collaboration with the Molecular Imaging and Targeted Therapeutics laboratory to identify imaging biomarkers of tumour response to novel targeted therapies. In complementary studies, whole-body autoradiography together with high-resolution micro-autoradiography are then used to define the biodistribution of radiolabelled compounds in vivo.
Specific activities include:
- Using in vitro assays and in vivo models for pre-clinical drug evaluation.
- Developing in vitro and in vivo models pertinent to the evaluation of novel anti-cancer drugs.
- Using PET imaging for assessment of tumour response to novel targeted therapies.
- Interaction with academic laboratories, biotechnology companies and the pharmaceutical industry.
Translational Cancer Biology
The CRC for Cancer Therapeutics Translational Cancer Biology team contributes to the development of new small molecule-targeted therapies for cancer by integrating cell biology, molecular biology and pre-clinical small animal imaging. The research group focuses on three main lines of investigation: developing specific strategies to assess cell-based potency of small molecule drug candidates; developing pharmacodynamic and predictive biomarkers of response to novel therapeutics; and selecting in vivo models of cancer to provide proof-of-concept efficacy data, with a particular focus on the use of non-invasive imaging technologies.
Through this research, the team contributes to the assembly of a data-rich pre-clinical compound brochure as a forerunner to compound licensing for late-stage pre-clinical and clinical assessment. The research team, led by Dr Nicole Haynes, works together with other CRC for Cancer Therapeutics research groups and a broad array of enabling technologies to interrogate these processes, including human xenograft and in vivo syngeneic tumour models, genetic modification of cancer cell lines, in vivo imaging using fluorescence and bioluminescence modalities, microscopy, immunohistochemistry and quantitative protein analysis.
Specific activities include:
- Developing and testing small molecule inhibitors of novel cancer targets.
- Identifying and validating biomarkers to predict response to targeted therapeutics.
- Understanding the mechanisms of action of therapeutics targeting signalling, cell cycle and cell surface receptors.
Young RJ, Bressel M, Porceddu S, Cernelc J, Savas P, Liuc H, Urban D, Thai AA, Cooper C, Fua T, Neeson P, Rischin D, Solomon B (2020). Validation and characterisation of prognostically significant PD-L1+ immune cells in HPV+ oropharyngeal squamous cell carcinoma. Oral Oncology. Volume 101. DOI: 10.1016/j.oraloncology.2019.104516
Solomon B, Young RJ, Bressel M, Urban D, Hendry S, Thai A, Angel C, Haddad A, Kowanetz M, Fua T, Corry J, Fox S, Rischin D (2018). Prognostic Significance of PD-L1+ and CD8+ Immune Cells in HPV+ Oropharyngeal Squamous Cell Carcinoma. Cancer Immunology Res. Jan 29. doi: 10.1158/2326-6066.CIR-17-0299. [EPub ahead of print]
Fleming CL, Natoli A, Schreuders J, Devlin M, Yoganantharajah P, Gibert Y, Leslie KG, New EJ, Ashton TD, Pfeffer (2019). Highly fluorescent and HDAC6 selective scriptaid analogues. Eur J Med Chem. Jan 15; 162:321-333
Martin CA, Cullinane C, Kirby L, Abuhammad S, Lelliott EJ, Waldeck K, Young RJ, Brajanovski N, Cameron DP, Walker R, Sanij E, Poortinga G, Hannan RD, Pearson RB, Hicks RJ, McArthur GA, Sheppard KE (2018). Palbociclib synergizes with BRAF and MEK inhibitors in treatment naive melanoma but not after the development of BRAF inhibitors resistance. Int J Cancer.142(10):2139-2152.
Trinkaus ME, Hicks RJ, Young RJ, Peters LJ, Solomon B, Bressel M, Corry J, Fisher R, Binns D, McArthur GA, Rischin D (2014). Correlation of p16 status, hypoxic imaging using [18F]‐misonidazole positron emission tomography and outcome in patients with loco‐regionally advanced head and neck cancer. Journal of Medical Imaging and Radiation Oncology. DOI: 10.1111/1754-9485.12155