Intra-tumor heterogeneity & treatment resistance in colorectal cancer metastasis | Melodie Grandin

By characterising intra-tumour heterogeneity using cutting edge technologies, we aim to find effective treatments for liver metastasis from bowel cancer through understanding how cells escape current treatments, and testing novel drugs on organoids – 3D tissue models grown from patient tumour samples.

Dr Melodie Grandin
Postdoctoral Fellow, Tumour Heterogeneity in Metastatic Cancer 
University of Melbourne Centre for Cancer Research and Department of Clinical Pathology

As a new starter with Associate Professor Frederic Hollande’s Tumour Heterogeneity in Metastatic Cancer lab, Dr Grandin will first present key data obtained during her previous research experience in France. She will cover how epidrug use promotes tumor sensitivity to dependence receptors induced apoptotic pathway. This work led to the development of a combined therapy based on the targeting of tumor cells exhibiting epigenetic alteration of the apoptotic pathway associated with Netrin-1, in subsets of patients with lung and breast cancers.

Dr Grandin will then present a project recently started in Australia, using 3D organoids derived from patients to unravel the intra-tumor heterogeneity and it’s dynamic during drug treatment. The group use several approaches including optical and genetic barcoding, single-cell RNA sequencing drug screens. This work will provide new insights on the dynamic process of tumor resistance to therapy, and will hopefully provide new therapeutic options for the treatment of patients with metastatic colorectal cancer.

Dr Melodie Grandin obtained a Masters degree in functional genetics and cellular pathology at the university of Lyon, in France, then followed by a PhD in molecular biology, oncology and cellular pathology at the cancer centre of Lyon in Patrick Mehlen’s laboratory. During these years, she described the epigenetic alterations of the Netrin-1 dependence receptor pathway and developed a combined therapy based on the transcriptional reexpression of key genes involved in apoptosis. This work has led to the publication of a few papers as a first author, including one in EMBO MM and one in Cancer Cell as well as a patent.

Dr Grandin recently started working at the UMCCR in Frederic Hollande’s lab thanks to a generous donation from John Landerer, and aim to unravel the cellular mechanisms driving intra-tumoral heterogeneity. To do so, the group are using cutting edge technologies and patient-derived organoids to improve our understanding of the subcellular processes driving drug resistance in advanced bowel tumours.