SEMINAR | Alex Caneborg PhD completion seminar

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine cancer of the skin, with Australia having the highest incidence globally. Despite historically having a poor prognosis, immune-checkpoint inhibitors (ICI) have proven to be highly efficacious, with 65% of patients experiencing disease control. However, ~50% of patients either don’t respond or progress on treatment, highlighting an unmet need to identify biomarkers of ICI response and acquired resistance.

In this seminar, Alex Caneborg will present his PhD spanning three thesis results chapters. The first chapter of his thesis explored the use of MCC cell lines that showed highly variable responses to type II interferon and ICI-treatment response in the clinic, leading to a hypothesis that epigenetic cellular programming of the cancer may be responsible for both the in vitro and clinical obervations. Here, Alex discovered promoter DNA methylation of the IFN-target gene IRF8 was associated with overexpression of a protein called osteopontin – known to have potent immune suppressive effect in the tumour microenvironment. The second chapter involved a broader molecular landscape analysis of MCC tumours with the hypothesis that distinct subtypes of MCC tumours exist that are important to understand the tumour heterogeneity and treatment response in patients. Here, Alex found 4 global and 3 skin-specific molecular subtypes of MCC showing associations with the viral aetiology of these cancers, immune marker enrichment and signaling pathways. The final research chapter explored the utility of ctDNA for monitoring ICI response. Alex investigated two contemporary tumour-informed methods comparing targeted variant panels and whole genome sequencing of cell-free DNA. Alex therefore discovered novel biology of MCC tumours and biomarkers of clinical importance that may in the future be useful to predict ICI response and track disease progression.

Alex is a PhD student in the Rare Disease Oncogenomics (RADIO) Lab at the University of Melbourne, led by A/Prof. Richard Tothill. Utilising a multi-omic framework across multiple genomics platforms, his work aims to interrogate the genomic landscape of Merkel Cell Carcinoma and identify mechanisms which influence its immune landscape and subsequent immunotherapy response.

This seminar will be held on December 11 in Lecture Theatre B, Level 7 VCCC in-person and via Zoom between 11:30am-12:30pm.

The seminar will be followed by light refreshments in the atrium.

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