Posted: 18 September 2023
The United States Department of Defense has called on Peter Mac to help in its fight against melanoma, granting a million dollars to researcher Dr Lorey Smith.
Melanoma is of particular interest to the U.S. military because active-duty service members spend prolonged periods outside, especially during deployment – the greatest incidence rates in the Air Force, Navy, and the Marines.
This has led to the development of its Melanoma Research Program – with the DOD funding leading research across the globe that will benefit both its service personnel and society at large.
Despite decades of research into how melanoma cells spread from primary tumors to other tissues, the ability to predict which patients will ultimately relapse, and options to prevent this, remain limited.
Dr Smith won her US DOD Melanoma Research Program Idea Award to use a powerful new technology to identify molecular pathways that influence the spread of melanoma that can then be targeted to inhibit the cancer earlier in its progression.
“As melanoma cells metastasize, they undergo a series of cell state transitions that allow them to invade the surrounding tissue, enter the circulatory system before colonizing distant organs,” Dr Smith explains.
“Exposure to these distinct environments in the body requires the ability to adapt. Understanding the molecular features of the different stages of melanoma progression is key to unlocking biomarkers and therapies to prevent metastasis.
“Ultimately, we aim to discover new biomarkers and preventative therapeutics to stop melanoma in its tracks earlier and prevent recurrence.”
Dr Smith, a former Peter Mac Lea Medal winner and current Victorian Cancer Agency Mid-Career Fellow in the Molecular Oncology Lab, will work in collaboration with Peter Mac Head of Molecular Oncology Laboratory, Professor Grant McArthur, Peter Mac Head of Computational Biology Program, Professor Alicia Oshlack, and University of Melbourne Research Fellow Dr Michael Clark, on this research.
The project will apply a new and rapidly evolving sequencing technology which provides superior resolution of mRNA processing than previously available methods, to primary and early metastatic melanoma patient samples. The samples in the study have been generously donated by Melanoma Research Victoria (MRV), a melanoma biobank containing samples from over 3,500 melanoma patients.
mRNA – or messenger RNA – molecules work as the instructions our bodies need to make proteins for everyday functioning. Around 30 per cent more mRNA processing events happen in cancer cells compared to normal cells, however changes in mRNA diversity in cancer progression remains largely unexplored.
Dr Smith said the advantage of this new sequencing technology is that full-length mRNA molecules can be identified in high throughput, which has not been able to be achieved previously.
“Therefore, the full degree of mRNA diversity can be detected for the first time,” she said.
“The main objectives of this research are to determine the relationship between global changes in mRNA diversity and metastasis in melanoma patients, and to determine whether specific mRNA variants are predictive of melanoma progression, and if these can be targeted to prevent melanoma metastasis.”
This approach has strong potential to identify specific mRNA variants that can be targeted to prevent metastasis, which would introduce new candidate genes for preventative therapies. If successful, these findings will benefit melanoma patients diagnosed with stage I or II melanoma by generating new biomarkers that are predictive of metastatic progression.
In the long term, these studies may also identify new targets for preventative therapeutics for high-risk patients to prevent subsequent metastasis and improve outcomes for patients.
