Current projects

Melanoma Institute Australia has dozens of research projects going at any one time. These are just a few of note.

Melanoma Genome Project

Melanomas develop following the accumulation of genetic mutations that enable the cells to grow uncontrollably. The Australian Melanoma Genome Project is using cutting-edge whole genome sequencing technologies to identify the common genetic mutations that cause melanoma so that doctors can better personalise its treatment.

The project has made major progress by comparing the genetic code of normal cells and melanoma tumours and identifying all the mutations present in nearly 500 Australian melanoma patients. It is the largest melanoma research effort ever undertaken in this country, with a national coalition of over 50 researchers from Melanoma Institute Australia, The University of Sydney, Royal Prince Alfred HospitalWestmead Institute for Medical Research and the QIMR Berghofer Medical Research Institute working together.

Purpose

  1. Fully characterise all the genomic alterations in over 500 melanomas patients (currently 468 melanomas sequenced). 
  2. Identify mutagenic processes and carcinogens responsible for the development of a range of melanomas.
  3. Discover new drug targets and better select patients for current therapeutics.

Highlights so far

Current projects

Funding

The Australian Melanoma Genome Project was funded directly by Melanoma Institute Australia, the NSW Ministry of Health, Cancer Council NSW and the Australian Government through Bioplatforms Australia.

The project has been enabled by Program Grants and Fellowships of the National Health and Medical Research Council, Translational Program Grants of Cancer Institute NSW, and infrastructure of the University of Sydney, Bioplatforms Australia, Westmead Institute for Medical Research, NSW Health Pathology, Royal Prince Alfred Hospital, Peter MacCallum Cancer Institute, The Olivia Newton-John Cancer Research Institute and Melanoma Institute Australia.

Project leads

From Melanoma Institute Australia:

From QIMR Berghofer Medical Research Institute:

 

Predicting response to immunotherapy

To realise the promise of personalised medicine, clinicians need to know ahead of time which patient with melanoma will respond to which therapy. Currently, a set of genetic signatures are used as molecular biomarkers to predict therapeutic response.

One highly successful immunotherapy, in patients who do respond to it, is the anti-PD1 antibody MK-3475. PD1 is a protein (programmed death) which is expressed on the surface of immune cells to form a biochemical shield protecting melanoma cells from the immune system. Deploying an antibody to PD1 blocks this protective action. But this only works in 60% of patients.

This research project involves working with tissue samples from the MIA Biospecimen Bank donated by patients treated with MK-3475, both responders and non-responders. The RNA is first extracted from the samples, followed by sequencing using advanced high-throughput technologies to profile differentially expressed genes which are associated with good response to anti-PD1 immunotherapy. 

Already, a list of genes has been identified which distinguish good and poor response for anti-PD1 immunotherapy. The next step is to tease out the biochemical and immune signalling pathways these genes are affecting.

Adjuvant Therapy Clinical Trial

MIA is experiencing great success with multi-discipline trials in the neo-adjuvant and adjuvant settings.

In high risk Stage III patients (where the melanoma has travelled to lymph nodes), a combination of two targeted therapies is given for 12 weeks prior to lymph node removal surgery, with the aim of shrinking the tumour to facilitate as easy and simple an operation as possible, and to prevent the risk of recurrence (normally around 50%). Following surgery, the same therapies are given for another 40 weeks (in total, drug therapy is received for 52 weeks). An interim analysis presented at ASCO in June 2016 revealed the fantastic news that at the point of surgery, all patients had marked tumour reduction or complete disappearance on scans, and around 50% of patients had no melanoma cancer cells left in their tissue.

The protocol has been further developed to investigate the next stage of this promising approach. The Neo-Trio trial, which will commence recruitment in 2017, will test whether treating Stage III melanoma
patients with either immunotherapy or immunotherapy plus targeted therapy before and after complete lymph node dissection can prevent Stage IV melanoma from developing. This will be revolutionary if it
works.

Surgery Support Clinic

One of the most significant surgeries which has to be performed in patients with melanoma which has spread to lymph nodes is an ilio-inguinal dissection. This operation involves taking out affected lymph nodes in the groin and the pelvis. It entails a week in hospital, followed by four to six weeks’ convalescence and up to six months for full recovery. This surgery can have wide-ranging physical impacts including lymphoedema (swelling of a limb) but also impacts on family life, work, psychological state and more.

Thanks to a two-year grant from Friends of the Mater, MIA is conducting qualitative research to determine the value of providing such patients with the services of a dissection clinic. The clinic is offered to patients who have undergone groin dissection as well as lymph nodes removed from the armpit (axillary dissection) or the neck (neck dissection) if the melanoma has spread to these areas. The clinic provides physiotherapy to assist with lymphoedema assessment and an ongoing relationship with a surgical clinical nurse consultant (CNC). The CNC offers information regarding the surgery, its effects and guidance about how best to navigate its impact on life. The CNC first sees the patient prior to the surgery and then in hospital and subsequently in the clinic at varying intervals. 

Patients were surveyed before and after their surgery using a quality of life survey and a depression scale. A similar study was conducted with a cohort of patients who did not have access to the dissection clinic, for comparison purposes. Detailed analysis of the results is still pending, but early findings show that patients facing dissections find the clinic extremely valuable and need such services for up to a year. Without such a clinic, their experience is typically that they do not cope very well after the surgery. Earlier referrals for lymphoedema treatment and also to a psychologist may also be beneficial.

Patterns of Care

This is a population-based, observational study based on clinicians’ reported management over a 12-month period of melanoma patients across New South Wales. The aim was to assess the patterns of medical care for patients against best practice guidelines and identify any variations and therefore areas for improvement. Once the Cancer Registry received notification of a new diagnosis of melanoma, the referring doctor was sent a questionnaire and similarly with any other
clinicians subsequently involved in the patient’s care. Over 70% of clinicians responded and almost 4,000 questionnaires were received, providing data for about 2,700 patients.

This has been an ambitious and very productive study done in collaboration with The NSW Melanoma Network with three papers accepted, another two under revision with the journal and three more in preparation. Just a handful of the more interesting findings include:

  • Adherence to clinical guidelines for surgical management and follow-up is not what it should be. Surgical margin guidelines were only adhered to in 35% of cases, while 45% were over-treated and 21% under-treated. Such factors as clinician caseload, age and socio-economic status of practice location were associated with variations.
  • 74% of patients’ doctors were aware of their risk factor status with respect to personal and family history of melanoma and the presence of moles. Doctors were more likely to know the family history of younger melanoma patients (under 40) than those over 80 and were more likely to give early detection advice to the younger age group.
  • Clinical management of higher risk patients was more likely to conform to best practice guidelines for diagnosis and skin surveillance than that of lower risk patients.

Saving Our Next Generation

Melanoma is the most prevalent cancer in 20-34 year olds. And traditional treatments like, chemotherapy and radiotherapy, can cause longterm damage to growing bodies.

Postdoctoral Fellow, Dr James Wilmott is hoping to help by searching for early-detection genetic markers and treatment options that are specific to this age group.

“New drugs that target genetic mutations specific to a patient’s melanoma look extremely promising. But young patients have been largely overlooked in this kind of research. This study will address that gap by characterising all the gene mutations in blood and melanomas from young people with melanoma.”

Dr James Wilmott

 

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The study is the first of its kind in the world. Data benefitting a range of research groups will be made available in Australia and abroad, bringing together pathologists, oncologists, surgeons, epidemiologists, computational biologists and researchers to focus on youth melanoma.

The goal is to identify the best genes for new drugs to target and uncover genetic mutations that predispose young patients to melanoma. It’s a unique and inventive way to detect melanoma in young people. And it will have the side benefit of helping them understand the benefits of sun safe behaviour and regular skin checks to reduce their risk of melanoma.

The data generated by the project will ensure that young melanoma patients are not left behind in innovations in personalised medicine, making a real difference to people in the prime of their lives.