Discovered one cause and one possible treatment of metastatic melanoma

Metastatic melanoma cell analysed on the study.
Metastatic melanoma cell analysed on the study.
Research
(02/06/2015)

Metastasis causes 90% of deaths in cancer patients. Therefore, one of the priorities in cancer research is to understand the mechanisms underlying this process. Metastasis occurs when tumour cells break away from the part of the body where cancer started to other parts of the body, invading nearby tissues and spreading to other body organs. Melanoma is one of the tumours with the highest ability to produce metastasis. Melanoma incidence has increased for the last decades as a consequence of higher sun exposure.

 

 

Metastatic melanoma cell analysed on the study.
Metastatic melanoma cell analysed on the study.
Research
02/06/2015

Metastasis causes 90% of deaths in cancer patients. Therefore, one of the priorities in cancer research is to understand the mechanisms underlying this process. Metastasis occurs when tumour cells break away from the part of the body where cancer started to other parts of the body, invading nearby tissues and spreading to other body organs. Melanoma is one of the tumours with the highest ability to produce metastasis. Melanoma incidence has increased for the last decades as a consequence of higher sun exposure.

 

 

The study, described in 1 June 2015 issue of the journal Nature Medicine, has been led by Manel Esteller, professor of Genetics at the University of Barcelona (UB) and ICREA research professor at the Bellvitge Biomedical Research Institute (IDIBELL). It describes a mechanism that explains how tumour cells break off from the main tumour and travel to other tissues and organs, thus producing metastasis. In addition, it points out that metastatic cellsʼ may be susceptible to new molecular treatments.

“We compared patientsʼ original tumour cells with metastatic cells and we observed that the latter ones have a specific alteration in their genetic material. To be exact, they activate a gene which is silenced both in healthy and primary tumour cells”, explains Esteller, director of the Epigenetics and Cancer Biology Programme at IDIBELL. “This gene acts as a light bulb that guides tumour cells when they break away from the place where cancer first started”, says the researcher.

The gene, named TBC1D16, regulates powerful oncogenes like BRAF and EGFR. “It is particularly interesting —emphasizes Manel Esteller—, that metastatic melanoma gets addicted to these oncogenes, so target drugs, named BRAF and MEK inhibitors, are more effective”.

According to IDIBELL researcher, “the study proves that human tumours change throughout their natural history by means of genome regulation (due to epigenetic changes) in order to adapt and survive in invaded tissues”. The study is even more relevant as “it suggests that combined treatments that hinder tumour cells adaptation are the most suitable to treat the disease”.
 
Article reference:
Vizoso, M.; Ferreira, H. J.; Lopez-Serra, P.; Carmona, F. J.; Martínez-Cardús, A.; Girotti, M. R.; Villanueva, A.; Guil, S.; Moutinho, C.; Liz, J.; Portela, A.; Heyn, H.; Moran, S.; Vidal, A.; Martínez-Iniesta, M.; Manzano, J. L.; Fernández-Figueras, M. T.; Elez, E.; Muñoz-Couselo, E.; Botella-Estrada, R.; Berrocal, A.; Pontén, F.; Van den Oord, J.; Gallagher, W. M.; Frederick, D. T.; Flaherty, K. T.; McDermott, U.; Lorigan, P.; Marais, R.; Esteller, M. “Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Nature Medicine, June 2015. Doi: 10.1038/nm.3863