Botella-Estrada R, Sanmartín Jiménez O
Instituto Valenciano de Oncología, Valencia, España.
Actas Dermosifiliogr. 2010 Jun;101(5):394-400.
A number of molecular alterations have been described for melanoma. Melanomas with BRAF mutations tend to be located in areas of intermittent sun exposure, whereas melanomas with KIT mutations mostly appear in acral areas, the mucosas, and areas of chronic sun exposure. Sorafenib, a BRAF inhibitor, has a cytostatic effect on most melanomas with mutations affecting the mitogen-activated protein kinase (MAPK) pathway, and is also capable of triggering apoptosis in a small subgroup of these melanomas. By inhibiting KIT, imatinib has a cytostatic and cytotoxic effect on melanomas with KIT mutations, and probably has the same effect on another subgroup of melanomas with other as yet imperfectly understood KIT mutations. For therapy to be effective, agents should be selected according to the pathways associated with the genetic mutations present in the melanoma.
黑色素瘤已被描述出多种分子改变。具有BRAF突变的黑色素瘤往往位于间歇性阳光照射区域，而具有KIT突变的黑色素瘤大多出现在肢端部位、黏膜以及慢性阳光照射区域。索拉非尼是一种BRAF抑制剂，对大多数影响丝裂原活化蛋白激酶（MAPK）途径的突变黑色素瘤具有细胞生长抑制作用，并且还能够在这些黑色素瘤的一小部分亚组中引发细胞凋亡。通过抑制KIT，伊马替尼对具有KIT突变的黑色素瘤具有细胞生长抑制和细胞毒性作用，并且可能对另一组具有其他尚未完全了解的KIT突变的黑色素瘤亚组具有相同作用。为使治疗有效，应根据与黑色素瘤中存在的基因突变相关的途径来选择药物。
