GARVAN Institute – Cancer Drug Resistance Research 2015-2017

The GARVAN Institute of Medical Research is a multi-disciplinary facility with more than 600 scientists and PhD students working across five major divisions: Bone Biology, Cancer, Diabetes and Metabolism, Immunology, and Neuroscience.

In 2012 GARVAN and St Vincent’s Hospital opened The Kinghorn Cancer Centre in Darlinghurst. This new facility brings researchers and clinicians together allowing clinical challenges to directly drive laboratory research and research findings to be rapidly translated into the clinic for prevention, diagnosis and treatment of individual cancer patients. The Kinghorn Cancer Centre promises to revolutionise cancer treatment through its use of ‘personalised medicine’ – the right treatment for the right person at the right time. The major challenge facing ‘personalised’ medicine is drug resistance, ultimately leading to drug failure and death. The basic principles behind resistance are surprisingly poorly studied at the genomic level.

A post-doctoral fellow in Professor David Thomas’ laboratory, Dr Arcardi Cipponi, has developed a model for observing the ‘morphing’ of cancer genomes under intense evolutionary selection pressure – specifically, anticancer drugs in or coming into clinical use. Dr Cipponi has already accumulated excellent data that cancer gnomes ‘wake up’ when exposed to a variety of drugs, and start to change dramatically. To this point his analyses have used existing tools.

His research will be taken to the next level by whole genome sequencing the existing cell models before, during and after drug selection and resistance. This program will utilise the cutting-edge whole genome sequencing technology (HiSeq X Ten) that has been recently acquired by GARVAN. Specifically, the Girgensohn Foundation, in its first year,  supported these analyses on 50 cell populations representative of cancers targeted in the clinic.

The outcome of this work is fundamental to all cancers. If realised, the current static ‘snapshots’ of cancer genomes will be replaced by ‘movies’, which show us for the first time how these malignant species evolve to survive all attempts to achieve cure.

After six years of work there is compelling evidence of common mutational mechanisms used by neoplastic cells to evade anti-cancer treatments. Experiments are ongoing. A summary is currently being prepared and a number of opportunities to propel this research are explored.