This project is focused on improving the treatment successfor skin cancerpatients. Throughutilisinggenome sequencing technology, advanced imaging techniques and novel drug targeting applications, this project will analyse the effectiveness of specific therapeutics upon individual skin cancer patients within a powerful 3D invasion system.

Skin cancer arisesdue to the development of abnormalcellsthat have the ability to invade orspread to other parts of the body.There are three main types: basal cell cancer(BCC), squamous cell cancer(SCC) andmelanoma. Greater than 90% of cases are caused by exposure toultra-violet (UV) radiationfrom the sun.This exposure isincreased in Australia due to a large hole in our ozone layer, directly above. Thus, skin cancer accounts for 80% of all new cancers diagnosed each year in Australia, with Australians having the highest rate of melanoma in the world.

Established approaches to treat melanomaare largely ineffective, due to the genetic mutation in melanoma (highest of all cancer types).This has led to extensive research into understanding melanomaat a genomic level and the surrounding normaltissue and vasculature that dictate the invasive capacity of apatient’s unique tumour mass.

2D experimentation (cancer cells in a petri dish) is the most commonresearch method initially undertaken to understandthe cytotoxic or inhibitory effect of novel compounds on cancer cell death. However, thisdoes not accurately model thecomplex three-dimensional environment of cancer invasion and spread (also known as metastasis), as occurs in the human body. Cancer invasion and metastasis are influenced by the surrounding normal cells, governing individual and collective cell behaviour. The cancermicroenvironment contains lots of different cells, like white blood cells and vascular cells, as well as proteins that make up the scaffolding for the cells within a specific tissue area.Thus, this microenvironment constitutes the backdropon which the hallmarks of every patients cancer can evolve.

In order to control a malignancy, it is therefore necessary to target and control the growth, invasion and spread of the cancer cells through modifications within this microenvironment. In order to further understand the crosstalk between skin cancer cells and thismicroenvironment, this project will examine the impact of the microenvironment within a 3D setting, allowing us to examine the aberrant regulation of critical events that lead to the first cancer cells separating andmetastasising from the primary tumour.

Through using this 3D tumor invasion model, in conjunction with advanced imaging techniques, we are discoveringdetailed mechanistic information on tumour invasion, migration and drug response. This powerful novel system emulatesthe environment thatoccurs in the human body during cancer growth and invasion. Thus, this technique will allow fordrug response testing on specific patient tumour samples, allowing us to gauge treatment effectiveness uponcancer cell migration withinpatientspecific cancerstates.

Finally, understanding skin cancer at a genomic level, will allowfor an increased understandingin drug response prediction. This project will utilise genome sequencing technology to annotate the specific gene mutationsofpatient skin tumour samples and store these ontoa database. This database will also collate the effectiveness ofboth conventional and novel targeted therapies upon skin cancer cell migration. Thus, this project will help to improvetreatment options for eachspecific skin cancer patient and provideessentialdata for more effective treatment plans for future skin cancer patients.

We need that skrillah to stop this killer!