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International study improves understanding of melanomas

An international study has gained an unprecedented insight into the cellular makeup and activity of melanomas, paving the way for treatments to be better targeted at individual patients.

The study was led by scientists at the Broad Institute of Harvard and MIT and involved Dr Ken Dutton-Regester from the QIMR Berghofer Medical Research Institute Oncogenomics laboratory, who is currently on secondment at the Dana-Farber Cancer Institute in Boston.

The findings have been published in the journal Science.

The researchers used a cutting-edge technique, known as single-cell RNA sequencing, to genetically sequence 4,645 cells from 19 melanomas.

“When researchers genetically characterise tumours they’ve traditionally used a process known as bulk tumour sequencing,” Dr Dutton-Regester said.

“It’s the equivalent of putting all the cells in a blender; although you get an overview of what’s going on in the cancer, it also means you can miss out on a lot of important information.

“In contrast, the method we used allowed us to isolate individual cells within a melanoma – including cancer and immune cells – and look at what each one of them was doing. This is the most detailed view that’s ever been gained into the ecosystem of a melanoma.

“This process has given us a better understanding of how all the different cells in a melanoma are interacting with each other.

“Importantly, this analysis is helping us understand how the makeup of a melanoma influences its response to treatments, including why some patients become resistant or fail to respond to some drugs.”

In the last five to six years, two types of melanoma treatments have emerged: targeted therapies, which are designed to target genetic mutations in melanomas; and immune drugs, which allow a patient’s immune cells to recognise and destroy cancer cells.

However, nearly all patients will eventually become resistant to the targeted therapies and it is currently difficult to determine how patients will respond to the immune drugs.

“Melanoma cells can be in two different states. When they’re in one of these states, the cells, which are known as AXL-high cells, are resistant to targeted therapies,” Dr Dutton-Regester said.

“In this study, we’ve found that all melanomas contain AXL-high cells. From our results we think that the presence of these cells in all melanomas might contribute to the widespread drug resistance we eventually observe in the majority of patients.

“This finding has given us a better understanding of how melanomas may be responding to this treatment and, looking to the future, may help inform us of alternative strategies to combat drug resistance in order to improve patient survival.

“This study has also given us a better understanding of what immune cells are doing within a melanoma, which may in future help us to predict how well a person is likely to respond to immune treatments.”