Cappuzzo F, Toschi L, Finocchiaro G, Ligorio C, Santoro A
Department of Oncology-Hematology, Istituto Clinico Humanitas IRCCS, Rozzano, Milan, Italy.
Int J Biol Markers. 2007 Jan-Mar;22(1 Suppl 4):S10-23.
The epidermal growth factor receptor (EGFR) plays a key role in cancer development and progression in several human malignancies including non-small cell lung cancer (NSCLC). Several strategies aimed at inhibiting the EGFR have been investigated in the last years, including the use of small tyrosine kinase inhibitors (TKIs) directed against the intracellular domain of the receptor and monoclonal antibodies targeting its extracellular portion. Subgroups of patients who are more likely to respond to TKIs have been identified based on both clinical and biological features. Never-smoking history has emerged as the most relevant clinical characteristic predictive of response to TKIs in NSCLC, while presence of drug-sensitive EGFR mutations and EGFR gene gain represent critical biological variables associated with an improved outcome for patients exposed to these agents. Recent studies have highlighted the existence of biological factors involved in intrinsic and acquired resistance to TKIs, including k-ras, HER-2 and EGFR exon 20 mutations. Increasing knowledge of EGFR biology and drug-receptor interactions will allow to identify individuals who are likely to derive a clinical benefit from the proposed targeted therapy, sparing refractory patients expensive and potentially toxic treatment.
表皮生长因子受体（EGFR）在包括非小细胞肺癌（NSCLC）在内的多种人类恶性肿瘤的发生和发展中起着关键作用。在过去几年中，人们研究了几种旨在抑制EGFR的策略，包括使用针对受体细胞内结构域的小分子酪氨酸激酶抑制剂（TKIs）和靶向其细胞外部分的单克隆抗体。基于临床和生物学特征，已经确定了更可能对TKIs有反应的患者亚组。从不吸烟史已成为NSCLC中预测对TKIs反应的最相关临床特征，而药物敏感的EGFR突变和EGFR基因扩增的存在是与接受这些药物治疗的患者预后改善相关的关键生物学变量。最近的研究强调了参与对TKIs的内在和获得性耐药的生物学因素的存在，包括k-ras、HER-2和EGFR外显子20突变。对EGFR生物学和药物-受体相互作用的了解不断增加，将有助于识别可能从提议的靶向治疗中获得临床益处的个体，避免难治性患者接受昂贵且可能有毒的治疗。
