Newer opportunities in systemic therapy of lung cancer.
Newer opportunities in systemic therapy of lung cancer.
复制标题
肺癌全身治疗的新机遇。
DOI：
10.1093/annonc/mdn445
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Giaccone,G
中科院分区：
文献类型：
--
作者：
Rajan,A;Gutierrez,M;Giaccone,G
Lung cancer continues to be the leading cause of cancer mortality despite steady improvements in treatment modalities over the last few years. Five-year survival remains unacceptably low at about 15%. Most patients who present with advanced disease can only be treated with palliative intent since the disease is not curable at this stage. Patients with locally advanced or metastatic disease are treated with systemic chemotherapy if they have a good performance status. First-line therapy consists of a platinum-based doublet, with or without bevacizumab, depending on histology and bleeding risk. In recent years a wealth of knowledge has become available on the molecular alterations associated with the development of lung cancer. Based on our understanding of the biology of lung cancer, targeted therapies have been developed and incorporated into currently existing treatment regimens. The most important examples that illustrate this fact are the anti-angiogenic agents such as bevacizumab and the epidermal growth factor receptor (EGFR) antagonists such as erlotinib. However despite these advances it is becoming increasingly clear that lung cancer is a complex disease, or indeed a heterogeneous group of diseases at the molecular level. Therefore, to develop truly effective systemic therapies, it is absolutely essential to know the molecular pathogenesis of the disease. The aim of this review is to illustrate key molecular pathways responsible for development of non-small cell lung cancer (NSCLC), and the way that drugs have been developed against potential targets involved in these pathways. epidermal growth factor receptorA key contributor to malignant transformation leading to lung cancer is EGFR. The EGFR is a member of a family composed of four receptors; EGFR (also known as ERBB1 or HER1), HER-2 (or ERBB2), HER3 and HER4 [1]. Aberrant functioning of these transmembrane receptor tyrosine kinases (RTKs) leads to activation of intracellular signaling cascades leading to cell proliferation and survival. EGFR is overexpressed in about 70% of NSCLCs and HER2 is overexpressed in about 30% of NSCLCs [2]. In addition, mutations have been described in the tyrosine kinase domain of EGFR in about 10% of NSCLCs in Caucasians and 25–50% in Asians [3]. Mutations and amplification of HER2 are very rare in NSCLC. Single-agent tyrosine kinase inhibitor (TKI) therapy against EGFR (gefitinib and erlotinib) has yielded response rates of 10–18%[4]. The only positive randomized phase III trial of TKIs administered in
