26/01/2012

The treatment of the melanoma with BRAF inhibitors has obtained big successes but it has taken as a not wished effect the development of secondary tumours, scaly carcinomas well differentiated and queratoacantomas. An international study reveals the high frequency of mutations of RAS in this type of secondary cutaneous neoplasias to treatment anti-melanoma. RAS mutations, specially HRAS, are frequent in the cutaneous carcinomas of scaly cells and the queratoacantomas that many patients develop treated with BRAF inhibitors, according to a study that publishes The New England Journal of Medicine and in which participated former residents of Vall d'Hebron University Hospital of the service of oncology, as Dr. Antoni Ribas, nowadays in the University of California, and of the service of dermatology directed by the Dr. Vicente García Patos, as Dr. Amaya Virós, now in the Institute of Cancer Research of London. As Dr. Virós explains, "we observe in the clinical trials that the patients were developing scaly carcinomas and queratoacantomas, epidermal tumours that can have a RAS mutation". BRAF's inhibitors can, in presence of a RAS mutation, disable the cells that depend on BRAF oncogene (melanoma) but paradoxically they can activate the cells that depend on the RAS oncogene (scaly carcinomas and queratoacantomas). The authors took "human samples of scaly and queratoacantomas of Roche's clinical trials where patients of melanoma were treated with BRAF inhibitors that developed scaly tumours, were sequenced and verified that they had RAS mutations in a high percentage ", assures Dr. Virós. To prove that this second neoplasia was arising as side effect of these new drugs, they compared mice with scaly tumors exposed to BRAF's inhibiting drug to a similar cohort not exposed to the drug. The mice exposed to the drug developed tumours much before than mice which weren't treated with the drug, reproducing the effects that were observed in human beings. Combinations of drugs were used in this model of mouse to delineate a therapeutic strategy that could remedy this side effect. In mice treated with BRAF inhibitors and MEK's inhibiting drug, another activator oncogene of the melanoma, it was possible to avoid the development of neoplasias scaly. This result means an evidence in vivo that this combination of drug might be profitable for patients of melanoma metastatic with BRAF's mutation.