Georgetown University Hospital, 3800 Reservoir Road NW, Washington DC 20007, USA.
Expert Opin Investig Drugs. 2011 Mar;20(3):415-22. doi: 10.1517/13543784.2011.557063.
EGFR targeting is a valid and vital approach in the treatment of patients with lung cancer. However, all patients treated with reversible inhibitors develop acquired resistance over time. It is of paramount importance that novel agents are designed and developed to overcome such acquired resistance.
The role of EGFR targeting in NSCLC, mechanisms of primary and acquired resistance to reversible inhibitors, and strategies to overcome resistance are examined. Preclinical and clinical data pertaining to BIBW 2992 in advanced solid tumors, and particularly in NSCLC, are also thoroughly reviewed. We hope that the reader will gain a comprehensive knowledge of the emerging field of resistance to EGFR inhibition, specifically relating to drugs being developed for lung cancer patients.
Irreversible dual inhibitors of EGFR-HER2 such as BIBW 2992 provide a promising approach to overcoming acquired resistance to erlotinib and gefitinib in lung cancer. It is yet to be seen whether the drug can overcome primary drug resistance or delay time to development of acquired resistance to EGFR-targeted agents in NSCLC.
EGFR 靶向治疗是治疗肺癌患者的有效且重要的方法。然而,所有接受可逆抑制剂治疗的患者随着时间的推移都会产生获得性耐药。设计和开发克服这种获得性耐药的新型药物至关重要。
检查了 EGFR 靶向治疗在 NSCLC 中的作用、对可逆抑制剂的原发性和获得性耐药的机制,以及克服耐药性的策略。还全面审查了与晚期实体瘤,特别是 NSCLC 中 BIBW 2992 相关的临床前和临床数据。我们希望读者能够全面了解针对 EGFR 抑制的耐药性这一新兴领域,特别是与为肺癌患者开发的药物相关。
EGFR-HER2 的不可逆双重抑制剂,如 BIBW 2992,为克服肺癌中厄洛替尼和吉非替尼的获得性耐药提供了有希望的方法。该药是否能够克服原发性药物耐药性,或者延缓 NSCLC 中针对 EGFR 靶向药物的获得性耐药的发生时间,还有待观察。