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Centenary Institute - Medical Research
Centenary Institute - Medical Research

Triggering melanoma cell death

Scientists at the Centenary Institute have reported a new strategy to battle melanoma, the most dangerous form of skin cancer, responsible for approximately 1,700 deaths in Australia each year.  

Using drugs to inhibit two separate proteins, the researchers found that they could effectively kill melanoma cells by inducing apoptosis (the process of cellular self-destruction that takes place when a cell is no longer needed). 

This new treatment strategy has the potential to benefit a subgroup of melanoma patients who do not respond to targeted therapies or immunotherapy.

“Provoking apoptosis has proven extremely difficult due to the high expression of anti-apoptotic or ‘protector’ proteins found in melanoma cancer cells,” said lead author of the study, Dr Hsin-Yi Tseng, Research Officer in the Melanoma Oncology and Immunology Program at the Centenary Institute.

“These protector proteins help the melanoma cell to survive, thrive, and in some cases to aid resistance against advanced medical drug treatments,” she said.

In the study, the researchers inhibited, in combination, the protein MCL1, together with proteins from the bromodomain and extra-terminal (BET) family. Both are known to have key roles in protecting and supporting melanoma cancer cells inside the body.

“Our research showed that combining BET and MCL1 inhibitors is highly effective at killing melanoma. The protective abilities of the BET and MCL1 proteins are decreased by the drug inhibitors and also induce the cancer cells to self-destruct,” said Dr Hsin-Yi Tseng.

Senior co-author on the study, Dr Jessamy Tiffen also from the Centenary Institute’s Melanoma Oncology and Immunology Program says the team’s research is highly significant and offers up a potential new treatment strategy for melanoma patients.

“Up to one half of melanoma patients do not respond to immunotherapy and a majority of patients tend to develop acquired resistance to targeted therapies. Our research examined a large number of human melanoma cell lines as well as use of mouse models. We saw extensive melanoma reduction in both cases which bodes well for the translation of this research into the next stage of development,” said Dr Tiffen. 

Read the full media release here.

Read the publication in the International Journal of Cancer here.

Centenary Institute’s rising stars

The Centenary Institute’s Dr Stefan Oehlers (Immune-vascular Interactions Laboratory within the Tuberculosis Research Program), Dr Jessamy Tiffen (Melanoma Oncology and Immunology Program) and Dr Hui Emma Zhang (Liver Enzymes in Metabolism and Inflammation Program) have all been named on the Educator’s list of Higher Education Rising Stars for 2020.

The list showcases individuals across the higher education spectrum who are making waves in the early stages of their careers and who have demonstrated leadership, innovation and achievement in their career to date.

Read more by clicking the link here:

International Women’s Day event

Dr Jessamy Tiffen from the Centenary Institute’s Melanoma Immunology and Oncology Program has participated in a special ‘Women in Education’ event held at Pymble Ladies College, Sydney.

Aligned with International Women’s Day, Dr Tiffen was an invited panel member at the event which was focused on inspiring female students as to the amazing wealth of opportunities and options available to women in the workplace.

Discussion, in a panel style Q&A format, covered the topics of women and education, leadership, potential discrimination and how to overcome it, as well as the importance of dreaming big for the future and setting achievable goals.

“It was absolutely fantastic to share my knowledge, issues I’ve experienced as a woman, as well to discuss my personal life and career journey to this group of incredibly interested students. There was genuine enthusiasm for what we were saying as panellists and some very insightful questions asked by these young women who are soon to embark on the next phase of their lives,” said Dr Tiffen.

Panel members at the event also included Dr Kate Hadwen, Principal, Pymble Ladies College and Caroline Gurney, Managing Director, Marketing & Communications, Asia Pacific, UBS. The panel moderator was Caroline Overington, Associate Editor, The Australian.

The ‘Women in Education’ event featured in the Australian newspaper and can be viewed here.

Connecting with the community

Some of our leading cancer researchers, Professor Phil Hansbro, Professor Peter Hersey, Dr Mainthan Palendira and Dr Jessamy Tiffen have presented their project updates and recent findings to consumers and supporters at our recent consumer engagement session.

The projects, all funded by Cancer Council NSW, covered the critical health areas of melanoma (the most deadly form of skin cancer) and lung cancer.

The engagement sessions allow Centenary scientists to connect directly with the community and  ensures that consumers are an integral part of the total research process.

Updates provided at the session were: 

  • Professor Phil Hansbro, Centenary Institute Deputy Director and Head of the Centenary UTS Centre for Inflammation. Could our gut bacteria play a role in lung cancer?
  • Professor Peter Hersey, Head of the Melanoma Immunology and Oncology Program / Dr Helen McGuire (University of Sydney). Epigenetic targeting of T cell dysfunction in patients failing immunotherapy
  • Dr Mainthan Palendira, Head of the Human Viral and Cancer Immunology Laboratory. The role of tumour-resident CD8+ T cells in metastatic melanoma and immunotherapy
  • Dr Jessamy Tiffen, Senior Research Officer in the Melanoma Immunology and Oncology Program. Place your BETs – Discovering new drug combinations for melanoma treatment

The Centenary Institute would like to thank all consumers and attendees at this session for their interest in improving human health outcomes, and continuing support of our life-saving medical research activities. 

New strategy to stop melanoma spread

Scientists from the Centenary Institute have developed a new therapeutic strategy that could potentially help the fight against advanced-stage melanoma.

In a study just released, the scientists were able to show that they could effectively reduce the migration and invasive properties of melanoma cells. This was achieved by successfully inhibiting the interaction between two proteins involved in intracellular trafficking (the process by which molecules cross the membranes of living cells).

The research is significant as metastasis–the process by which cancer moves to new areas of the body–is the leading cause of death in melanoma patients.

Published in the highly regarded Journal of Investigative Dermatology, the researchers first found that high expression of the protein melanophilin was indicative of poor prognosis in melanoma patients.

Employing human melanoma cell line models, the researchers were then able to demonstrate a significant reduction in the spread of cancer by blocking the ability of melanophilin to bind with the protein RAB27A (one of the critical regulators of intracellular transport).

“We have known for some time that the proteins melanophilin and RAB27A bind together and that this process could be crucial to help melanoma cells spread around the body,” said lead study author and Centenary Institute PhD researcher (Immune Imaging Program), Mr Dajiang Guo.

“By disrupting the binding of these two proteins with a recently developed blocking compound (BMD-20), we were able to successfully restrict the melanoma cell movement and invasion. What our findings suggest is that the development of new drugs that can specifically target melanophilin-RAB27A interactions are a promising target for advanced melanoma treatment,” he said.

Senior study author Dr Shweta Tikoo also from the Centenary Institute (Immune Imaging Program) notes that there is an unmet need for novel therapeutic strategies which can be developed as a standalone drug or as part of a combination therapeutic regimen in the battle against advanced melanoma.

“Melanoma has one of the highest mortality rates in the western world with the disease accounting for approximately 1,500 deaths in Australia every year. It is also the most common form of cancer affecting young Australians, those individuals aged from 15 to 39 years old,” she says.

Read the full media release here.

Read the publication in the Journal of Investigative Dermatology here.

House of Wellness – featuring Professor Peter Hersey

Professor Peter Hersey, Head of the Melanoma Oncology and Immunology Program at the Centenary Institute has been a guest on Macquarie Media’s ‘House of Wellness’ radio show.

The current focus of Professor Hersey’s research is to better understand the resistance of melanoma to new treatments.

On the show, Professor Hersey talked about the important need to protect ourselves against skin cancer by reducing sun exposure as we move into the summer months.

Click here to access the show and go to the 6.10 mark on the time code to hear from Professor Hersey.

Breakthrough in preventing the spread of melanoma

Researchers at the Centenary Institute in Sydney have led a study which has uncovered a brand-new target for melanoma metastasis; providing an improved understanding of how the cancer spreads and opening the door for more effective treatments.

Australia and New Zealand have the highest rates of melanoma in the world. More than 14,000 new cases of melanoma are estimated to have occurred in 2018.[1] Melanoma is the most common cancer in young Australians (aged 15-39), and it kills more young Australians than any other single cancer.

The primary cause of death in melanoma patients is metastasis – the process by which cancer spreads to other areas of the body. While there have been recent advances in targeted and immune-based treatments, advanced stage melanoma remains a clinical challenge with a particularly poor prognosis.

Scientists from the Centenary Institute, in collaboration with 11 other Australian research institutions, have identified a specific protein (called RAB27A) as a key driver of melanoma metastasis. This occurs via the secretion of pro-invasive exosomes; tiny bubble-like structures which are expelled from cells.

During the study, the researchers discovered that silencing the expression of RAB27A reduced a certain population of exosomes delivering pro-invasion messages, which led to reduced metastasis.

Lead author and PhD researcher in Centenary’s Immune Imaging Program, Dajiang Guo, says the discovery provides a new way through which researchers can better target and treat melanoma.

“From our findings, we propose RAB27A is a novel prognostic factor, which means it could provide clinicians with a new way to determine a melanoma patient’s future health outcome,” says Mr. Guo.

“We also believe it could provide a brand new therapeutic target for the prevention of metastasis, which would improve the efficacy of future treatments. This is significant because metastasis is the main cause of death in melanoma patients.”

 

View the full media release as a PDF.

Read the paper published in the International Journal of Cancer.

[1] The Australian Institute of Health and Welfare, Cancer Compedium: information and trends by cancer type.

Boosting the human body’s fight against melanoma

Scientists at Centenary have uncovered a new pathway in the body which fights cancer; paving the way for the development of drugs that improve the prognosis of patients with melanoma and other types of cancer.

“Sadly, Australia has one of the highest rate of melanoma in the world, with more than 1800 Australians dying from the disease each year. Our research has improved our understanding of how the body mounts the anti-cancer immune response but has also opened up ways scientists can develop new therapies to target this cell type in melanoma,” says Stuart Cook of Centenary’s Skin Imaging and Inflammation laboratory, the lead author on the paper.

Read the full media release.

Celebrating Australian luminaries who have transformed melanoma treatment worldwide

The extraordinary contribution of Australia’s most distinguished clinicians and researchers in the field of melanoma including Centenary’s Professor Peter Hersey was recently celebrated at a symposium hosted by the Melanoma Institute Australia (MIA).

More than 350 clinicians and researchers gathered at The Ultimate Melanoma Masterclass in Sydney to learn from the five luminaries as well as hear a comprehensive review on the latest advances in research and clinical management of melanoma.

Read the full article here