Rationale for targeting VEGF, FGF, and PDGF for the treatment of NSCLC.
Rationale for targeting VEGF, FGF, and PDGF for the treatment of NSCLC.
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DOI：
10.2147/ott.s18155
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发表时间：
2011
影响因子：
4
通讯作者：
Chachoua A
中科院分区：
文献类型：
--
作者：
Ballas MS;Chachoua A
肺癌仍然是全球死亡的主要原因，其中最常见的类型非小细胞肺癌（NSCLC）的5年生存率不到20%。虽然目前以铂为基础的双重化疗是晚期疾病的一线治疗方法，但它的临床获益有限，且有明显的毒性。为了克服这些限制，最近的研究集中在靶向治疗上，最近批准了靶向表皮生长因子受体和血管内皮生长因子（VEGF）信号通路的药物。然而，这些药物（吉非替尼、厄洛替尼和贝伐单抗）仅为一小部分患者提供抗肿瘤活性，肿瘤反应的患者不可避免地会对治疗产生耐药性。血管生成是肿瘤生长和转移的关键步骤，抗血管生成治疗可能具有抗肿瘤活性。开发新型抗血管生成疗法的重要靶点包括VEGF、成纤维细胞生长因子、血小板衍生生长因子及其受体。假设靶向多种血管生成途径不仅可以提高抗肿瘤活性，还可以降低耐药风险。一些新型药物，如BIBF 1120、索拉非尼、舒尼替尼和西地尼尼，在II期研究中显示出有希望的初步活性和耐受性，正在进行的III期随机研究的结果将需要确定这些新疗法在个体NSCLC患者管理中的潜在地位。
Lung cancer remains a leading cause of death globally, with the most frequent type, nonsmall cell lung cancer (NSCLC), having a 5-year survival rate of less than 20%. While platinum-based doublet chemotherapy is currently first-line therapy for advanced disease, it is associated with only modest clinical benefits at the cost of significant toxicities. In an effort to overcome these limitations, recent research has focused on targeted therapies, with recently approved agents targeting the epidermal growth factor receptor and vascular endothelial growth factor (VEGF) signaling pathways. However, these agents (gefitinib, erlotinib, and bevacizumab) provide antitumor activity for only a small proportion of patients, and patients whose tumors respond inevitably develop resistance to treatment. As angiogenesis is a crucial step in tumor growth and metastasis, antiangiogenic treatments might be expected to have antitumor activity. Important targets for the development of novel antiangiogenic therapies include VEGF, fibroblast growth factor, platelet-derived growth factor, and their receptors. It is hypothesized that targeting multiple angiogenic pathways may not only improve antitumor activity but also reduce the risk of resistance. Several novel agents, such as BIBF 1120, sorafenib, sunitinib, and cediranib have shown promising preliminary activity and tolerability in Phase II studies, and results of ongoing Phase III randomized studies will be necessary to establish the potential place of these new therapies in the management of individual patients with NSCLC.