Metastasis is responsible for 90% of deaths in patients with cancer. Therefore, understanding the mechanisms responsible for this process is one of the main goals of cancer research. Metastasis is a series of linked steps in which the primary tumor invades surrounding tissue and ends spreading throughout the body. One of the tumors with greater ability to metastasize is melanoma that has increased in incidence in recent decades, as a result of increased sun exposure.
Today, an article published in the journal Nature Medicine led by Manel Esteller, director of the Program Epigenetics and Cancer Biology (PEBC) of the Institute of Biomedical Research of Bellvitge (IDIBELL), ICREA researcher and professor of genetics at the University of Barcelona, It described a mechanism that explains how tumor cells escape from their place of origin metastasizing and also may be susceptible to respond to new molecular treatments.
"We have compared cells from the original tumor patients with cells that have metastasized and we have seen that the latter have a specific alteration in their genetic material. Specifically, activate a gene that is silenced in both healthy cells and cells of primary tumors, "explained Esteller.
"This gene" continues the researcher "lights up like a light bulb to guide tumor cells that escape the primary tumor."
The gene, called modular charge TBC1D16 powerful oncogenes such as BRAF and EGFR and what is "very interesting" says Esteller "is that melanoma metastases become addicted 'to these oncogenes so that drugs that are targeted, called BRAF and MEK inhibitors are more effective. "
Esteller explains "these studies confirm that human tumors in its natural history changed by adapting the regulation of its genome (epigenetic changes) to survive in new tissues where metastasize. But even more relevant, suggest that the use of combined treatments that do not allow the tumor cell are best adapted to treat the disease "
Vizoso M, HJ Ferreira, Lopez-Sierra P, Carmona FJ Martinez-Cardús A, Girotti MR, Villanueva A, Guil S, Moutinho C, Liz J, Portela A, Heyn H, S Moran, Vidal A, Martinez-Iniesta M Manzano JL, Fernandez-Figueras MT, Elez E, Muñoz-Couselo E, Bottle-Estrada R, Berrocal A Bridge F, J van den Oord, WM Gallagher, DT Frederick, Flaherty KT, McDermott U, Lorigan P, R Marais , Esteller M. epigenetic activation of a Cryptic TBC1D16 transcript Enhancer melanoma progression by targeting EGFR.
Nature Medicine, doi: 10.1038 / nm.3863, 2015.