- 20 September 2018
1:00 pm - 2:00 pm
Thursday 20 September 2018, 1.00 PM
Auditorium, Level 6, Bancroft Building
“We have to talk…” – Interactions during skin cancer metastasis
Dr Glen Boyle,
Cancer Drug Mechanisms,
QIMR Berghofer Medical Research Institute
Metastasis is the leading cause of mortality among cancer patients. While mutations in some genes driving metastasis have been identified, our mechanistic understanding remains incomplete. The group is interested in understanding the various processes, including communication between cancer cell populations, that occur during metastasis in particular of the different skin cancers. The presentation will touch on work in 2 different skin cancers namely squamous cell carcinoma (SCC) and melanoma. Squamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present such as perineural invasion (PNI). Awareness of perineural disease amongst clinicians and patients is limited. Our work has assessed the global gene expression differences between cSCCHN with or without PNI. Analysis showed signatures of gene expression that may indicate different forms of PNI result by different mechanisms. We have developed a mouse model to replicate the human disease progression, and will use this to further investigate the molecular pathway for development, and therapeutic options for PNI from cSCCHN. Melanoma tumours are highly heterogeneous, comprising of different cell types that vary in their potential for growth and invasion. Previous studies have shown mutually-exclusive expression of key transcription factors MITF and BRN2 has been identified in melanoma patient tumours. MITFhigh cells are thought proliferative, whereas BRN2high cells invasive. Our recent studies have shown that metastatic dissemination and subsequent growth of melanoma requires the expression of both transcription factors, thereby supporting the concept of heterogeneous co-operative invasion. Further investigation into BRN2-positive cells revealed a previously unknown role of the transcription factor in controlling a program leading to resistance to anoikis (cell death upon detachment). It may be possible to target these cells using therapeutic interventions.
Glen Boyle completed his PhD in the Department of Biochemistry and Molecular Biology at Monash University in 1999. He joined the Drug Discovery Group headed by Professor Peter Parsons at QIMR Berghofer, where he investigated development of skin cancer and melanoma, as well as novel anti-cancer agents including some aspects of the mechanism of action of PEP005 (Picato), a treatment now used for actinic keratosis. Boyle is currently a Group Leader and Head of the Cancer Drug Mechanisms Group in the Cancer Program, at QIMR Berghofer Medical Research Institute. Boyle established his group in as Team Head 2013, and continues his work as a Group Leader (2017). The group is interested in the molecular mechanisms of cancer progression and metastasis, and intrinsic drug resistance in heterogeneous tumour sub-populations. The group has also been involved in pre-clinical and mechanistic studies of a compound recently completed Phase I trials for treatment of cutaneous lesions including melanoma, skin and head and neck cancers.