Immunotherapy has transformed the treatment landscape for melanoma, giving hope to patients who previously had limited treatment options. Yet for many people, these treatments do not work as expected, or stop working over time.
With support from the Australian Melanoma Research Foundation, researcher Dr Laura Nicholls, under the supervision of Dr Jessamy Tiffen at the Centenary Institute and University of Sydney, has been investigating the biological mechanisms that help melanoma survive treatment.
The findings are helping researchers better understand how melanoma evolves, spreads and responds to therapy, paving the way for more personalised approaches to treatment in the future.
“We are extremely delighted to receive this research grant from AMRF. Despite enormous advances in melanoma treatments, the development of treatment resistance remains a major challenge that plagues long-term outcomes. This project offers hope for melanoma patients in improving long-term responses.”
Why Do Some Melanomas Stop Responding to Treatment?
Melanoma cells are remarkably adaptable. One of the ways they survive treatment is through a process known as phenotype switching, where cancer cells effectively change their identity to become more resistant to therapies designed to destroy them.
Dr Nicholls’ research focused on a gene called MECOM, which researchers suspected may play a role in helping melanoma cells adapt and survive.
The project set out to answer an important question: Could understanding MECOM help explain why some melanomas become more aggressive or resistant to treatment?
Using laboratory experiments and patient data, the research team explored how MECOM influences melanoma behaviour.
The findings revealed that higher levels of MECOM can help melanoma cells:
- Grow more rapidly
- Move more easily through surrounding tissue
- Better survive under stressful conditions
These are all characteristics associated with more aggressive cancers.
Interestingly, the research also showed that MECOM is not the primary driver of melanoma cell identity as originally suspected. Instead, it appears to play a supporting role, helping tumours survive and thrive under certain conditions.
One of the most promising findings emerged when researchers analysed data from melanoma patients.
The team discovered that patients with higher levels of MECOM were more likely to respond positively to anti-PD-1 immunotherapy, one of the most widely used treatments for advanced melanoma.
These tumours also showed evidence of a stronger immune response, suggesting MECOM may provide important clues about how the immune system interacts with melanoma.
In contrast, lower MECOM levels were more frequently associated with brain metastases, one of the most serious and difficult-to-treat forms of advanced melanoma.
These findings suggest MECOM could one day help identify patients who may be at greater risk of aggressive disease.
While further research is needed, the findings from this project could have important implications for melanoma care in the future.
MECOM may eventually help clinicians identify which patients are more likely to benefit from immunotherapy, allowing treatment plans to be tailored more effectively and understanding how MECOM influences melanoma behaviour could help guide the development of future therapies, particularly for patients whose cancers have become resistant to current treatments.
With support from AMRF, Dr Laura Nicholls successfully completed her Master’s research, contributing valuable new knowledge to the melanoma research community while building the skills and expertise needed to tackle future challenges in cancer research.
The project also enabled Dr Nicholls to present her work at the Australasian Melanoma Conference, helping share these findings with clinicians and researchers working to improve outcomes for melanoma patients.
The research team is now building on these findings through further investigation into MECOM and its role in melanoma progression and treatment response.
Thanks to the support of the Australian Melanoma Research Foundation community, researchers like Dr Laura Nicholls are helping uncover the answers that may one day lead to better treatments, more personalised care and improved outcomes for people affected by melanoma.
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