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Study identifies potential therapeutics target for metastatic melanoma

Researchers in the Randall Division of Cell & Molecular Biophysics have had the findings of their study into a potential therapeutics target for metastatic melanoma published in the journal Current Biology.

Entitled ‘TGFβ -induced transcription sustains amoeboid melanoma migration and dissemination’, the study aims to understand if the TGFβ protein has some impact in melanoma progression, especially during metastatic dissemination – when cancer spreads from one part of the body to another, unconnected part.

Metatasis is the cause of death in 90% cancer patients. In order to help develop anti-metastasis therapies, a greater understanding of the signals that drive metastasis at the molecular level is needed.

Melanoma is a very aggressive and invasive cancer which originates from melanocytes, pigment producing cells. The developmental origin of melanocytes is what is known as the neural crest, which is a very migratory cell population. Working on the belief that melanomas become very invasive because they retain in their memory the ability to migrate, this study wanted to understand if TGFβ had some impact in melanoma progression and especially during metastatic dissemination.

Whilst TGFβ is a factor that has multiple functions during embryonic development and in cancer, its function is not clear in melanoma. Researchers found that TGFβ drives a particular type of motility in melanoma cells that is very suited for fast dissemination. The study also unveiled all the molecules that work with TGFβ in melanoma and in particular CITED1. Melanoma patients with high levels of CITED1 have a worse prognosis that patients with lower levels, so being able to inhibit CITED1 function can make melanoma cells less invasive and less efficient in surviving in metastatic sites such as the lung.

The identification of CITED1 as a potential new therapeutic target for metastatic melanoma, could also mean it is used as a marker to identify a subset of patients whose tumours are highly reliant on TGFβ signalling and could be good candidates for drugs targeting this pathway.

Dr Vicky Sanz-Moreno said ‘Melanoma is one of the few cancers which is increasing in incidence. Metastatic melanoma is highly aggressive and even if there are very promising current therapies, there is still a group of patients that do not respond to treatment. Expanding our understanding of the disease and identifying new therapeutic targets for metastatic melanoma is therefore extremely important.’

Read the full paper.