The research focus of the Fox laboratory is to advance the field of molecular pathology in cancer.
- Discovery of novel markers and pathways implicated in angiogenesis/lymphangiogenesis in human cancer and its microenvironment (particularly hypoxia).
- Identifying biomarkers and pathways implicated in a number of tumour types, such as breast, lung, prostate and colorectal cancers.
- Identify methylation profiles and develop predictive and prognostic markers that can be used in diagnostic pathology.
- Cancer 2015 cohort project.
Angiogenesis and lymphangiogenesis
One of the main focuses in the laboratory is a global approach to identifying signalling networks in lymphatic endothelial cells using functional genetic screens. This project builds on a longstanding proven track record in angiogenesis research with co-investigators Profs Steven Stacker and Marc Achen. In contrast to normal tissue, the tumour microenvironment is often hypoxic and displays altered vasculature, contributing to an important role in cancer phenotype. Our studies encompass factors that affect lymphatic endothelial cell invasion and migration in the hypoxic tumour microenvironment.
Biomarkers and genomics
The recognition that cancer is a genetic disease has led to many candidate biomarkers being identified. Molecular pathology has thus become a pivotal discipline to determine their clinical utility. Through collaborations nationally and internationally, novel markers and pathways implicated in particular areas of tumour development and behaviour are assessed for their role in human cancer. The candidate genes are interrogated for their capacity to provide key diagnostic information for the development of both predictive and prognostic biomarkers across a number of tumour types, including breast, lung, prostate and colorectal. Promising candidates will be further assessed for their mechanistic role in cancer biology and disease by analysis in appropriate in vivo models via established and successful collaborations, with a view of identifying novel therapeutic targets.
Cancer 2015 project
Cancer 2015 was established in 2012 as a large-scale, prospective, longitudinal, multi-site cohort study of incident cancers in the Victorian population. Its goal is to create a world-class resource of comprehensive prospective information on 10,000 Victorians with cancer, regardless of type, to include clinical, genetic and health economic data to improve cancer care. In this project, not only will mutations be catalogued, but particular scientific questions and clinical issues regarding the molecular pathology of cancer will be addressed, which includes:
- Determining the number and frequency of actionable genetic mutations in tumours within the general population.
- The rate of genetic evolution during tumour development.
- The role of genetic mutations in tumour classification systems.
- Developing a clinical measure of tumour heterogeneity and evolution.
Find out more about Cancer 2015.
Deb S, Lakhani SR, Ottini L and Fox SB (2016). The cancer genetics and pathology of male breast cancer. Histopathology. 68(1):110-8.
Pang JM, Gorringe KL, Wong SQ, Dobrovic A, Campbell IG and Fox SB (2015). Appraisal of the technologies and review of the genomic landscape of ductal carcinoma in situ of the breast. Breast Cancer Res. 17:80.
Parisot JP, Thorne H, Fellowes A, Doig K, Lucas M, McNeil JJ, Doble B, Dobrovic A, John T, James PA, Lipton L, Ashley D, Hayes T, McMurrick P, Richardson G, Lorgelly P, Fox SB and Thomas DM (2015). “Cancer 2015”: A Prospective, Population-Based Cancer Cohort-Phase 1: Feasibility of Genomics-Guided Precision Medicine in the Clinic. J Pers Med. 5(4):354-69.
Doig K, Papenfuss AT and Fox S (2015). Clinical cancer genomic analysis: data engineering required. Lancet Oncol. 16(9):1015-7.
Wong SQ, Fellowes A, Doig K, Ellul J, Bosma TJ, Irwin D, Vedururu R, Tan AY, Weiss J, Chan KS, Lucas M, Thomas DM, Dobrovic A, Parisot JP and Fox SB (2015). Assessing the clinical value of targeted massively parallel sequencing in a longitudinal, prospective population-based study of cancer patients. Br J Cancer. 112(8):1411-20.
Pang JM, Deb S, Takano EA, Byrne DJ, Jene N, Boulghourjian A, Holliday A, Millar E, Lee CS, O’Toole SA, Dobrovic A and Fox SB (2014). Methylation profiling of ductal carcinoma in situ and its relationship to histopathological features. Breast Cancer Res. 16(5):423.
Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB and Achen MG (2014). Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer. 14(3):159-72.