Carlomagno Francesca, Chiariello Mario
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, via Pansini 5, 80131, Naples, Italy,
J Mol Med (Berl). 2014 Jul;92(7):723-33. doi: 10.1007/s00109-014-1177-7. Epub 2014 Jun 8.
Molecularly targeted cancer treatment has become an achievable goal thanks to systematic analysis of cancer genome as well as development of highly selective tumor targeted drugs. In many human cancers, deregulation of the RTK/RAS/MAPK pathway is the driving force of the disease. Indeed, cancer cells become addicted to such signaling, rendering them susceptible to drugs that can intercept growth factor signaling cascade at different levels. Discovery of mutations or aberrant expression of components of this cascade in radio- and chemotherapy refractory human melanoma acted as an enormous stimulus for scientist to try to identify and clinically test new therapeutic approaches blocking the RTK/RAS/MAPK cascade. These efforts not only resulted in the identification of new drugs for melanoma treatment but also in a better understanding of molecular basis of primary and secondary resistance to targeted therapies.
由于对癌症基因组的系统分析以及高选择性肿瘤靶向药物的开发,分子靶向癌症治疗已成为一个可实现的目标。在许多人类癌症中,RTK/RAS/MAPK信号通路的失调是疾病的驱动因素。事实上,癌细胞对这种信号传导产生依赖,使得它们易受能够在不同水平阻断生长因子信号级联反应的药物影响。在放疗和化疗难治的人类黑色素瘤中发现该信号级联反应成分的突变或异常表达,极大地刺激科学家尝试识别并临床测试阻断RTK/RAS/MAPK信号级联反应的新治疗方法。这些努力不仅带来了用于黑色素瘤治疗的新药,还加深了对靶向治疗原发性和继发性耐药分子基础的理解。