奥希替尼新辅助治疗ⅢA期EGFR突变肺腺癌后手术1例报道

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）已被批准用于非小细胞肺癌（NSCLC）治疗。本文报道1例42岁ⅢA期EGFR突变NSCLC男性患者,使用奥希替尼治疗4.5个月后切除肿瘤,术后继续奥希替尼辅助治疗,复查未见复发或转移,提示奥希替尼作为可切除Ⅲ期NSCLC的新辅助治疗可能有效。     

奥希替尼一线治疗EGFR突变型非小细胞肺癌脑转移患者的临床疗效

目的 探讨奥希替尼一线治疗表皮生长因子受体（EGFR）突变敏感的非小细胞肺癌（NSCLC）脑转移患者的临床疗效。方法 选取2018年1月至2021年8月在中南大学湘雅医院就诊的EGFR突变并接受奥希替尼一线治疗的NSCLC脑转移患者为研究对象。观察治疗3个月后所有患者的颅内客观缓解率（iORR）、颅内疾病控制率（iDCR），比较不同临床特征患者iORR和iDCR的差异；记录治疗期间不良反应发生率；随访所有患者治疗后疾病进展和死亡情况，并采用COX回归模型分析奥希替尼一线治疗的预后影响因素。结果 本研究共纳入82例NSCLC脑转移患者，接受奥希替尼一线治疗3个月后iORR为69.5%，iDCR为96.3%；不同年龄、性别、是否吸烟、PS评分、EGFR突变类型、脑转移部位、是否有其他部位转移、是否有中枢神经症状的NSCLC脑转移患者iORR和iDCR比较，差异均无统计学意义（P>0.05）；治疗期间不良反应总发生率为50.0%；总生存率为73.2%，无进展生存率为78.0%；COX回归分析结果显示，EFGR突变类型为L858R的NSCLC脑转移患者发生死亡的风险是19del突变患者的2.793倍（95% CI： 0.134~0.956， P=0.040），年龄>60岁的NSCLC脑转移患者发生死亡的风险是年龄≤60岁患者的4.385倍（95% CI： 1.267~15.175， P=0.020）。结论 奥希替尼一线治疗EGFR突变型NSCLC脑转移患者可获得良好的iORR和iDCR，且安全性较好。EGFR突变类型为L858R和年龄>60岁是NSCLC脑转移患者奥希替尼一线治疗的预后危险因素。     

尼洛替尼与伊马替尼治疗慢性粒细胞白血病早期临床疗效比较

目的 比较尼洛替尼与伊马替尼治疗慢性粒细胞白血病（CML）的早期（3个月时）疗效以及安全性。方法 选取2007年1月至2017年12月安徽省立医院确诊CML的患者129例,采用随机数字表法按照1∶7分为尼洛替尼组（18例）和伊马替尼组（111例）。两组患者服药3个月后门诊复查骨髓形态学、BCR-ABL融合基因国际标准值（BCR-ABL^IS）,比较两组患者的BCR-ABL^IS结果,评价两组患者的疗效（主要指标为BCR-ABL^IS≤10%的达标率、BCR-ABL^IS≤0.0032%的比例）以及药物的安全性（白细胞减少、血小板减少、贫血等血液学毒性;Q-T间期延长,以及肝功能损害、骨骼肌肉疼痛、水肿、皮疹、消化道症状等不良反应发生情况）。结果 尼洛替尼组患者治疗3个月时达到BCR-ABL^IS≤10%、BCR-ABL^IS≤0.0032%的比例均高于伊马替尼组（94.44%vs 69.37%;55.55%vs 27.92%）,差异均有统计学意义（P<0.05）;两组患者药物安全性比较,差异无统计学意义（P>0.05）。结论 尼洛替尼治疗CML的早期分子学反应达标率以及患者分子学反应的深度均高于伊马替尼组,两种药物不良反应发生情况无显著差异。     

盐酸埃克替尼治疗EGFR突变阳性非小细胞肺癌脑转移的近期效果分析

目的 探究盐酸埃克替尼对表皮生长因子受体（EGFR）突变阳性非小细胞肺癌脑转移的近期效果。方法 选取于南阳市中心医院肿瘤医院收治的EGFR突变阳性非小细胞肺癌脑转移患者共60例,所有患者均接受盐酸埃克替尼片口服治疗,125 mg/次,3次/d。回顾性分析其近期效果。结果 患者中位无进展生存期为12.6个月（95% CI 11.85~14.42）。所有患者均接受疗效评估,其中部分缓解（PR）23例,稳定（SD）37例,EGFR突变非小细胞肺癌（NSCLC）脑转移患者的有效率（ORR）为38.33%,疾病控制率（DCR）为100%。患者的治疗史、基因突变情况、性别以及吸烟与否与治疗无进展生存期（PFS）均无显著相关性（P>0.05）;患者的治疗史,性别与是否吸烟与ORR无显著相关性（P>0.05）,而患者的基因突变情况与ORR显著相关（P<0.05）。不良反应发生情况：皮疹共出现5例,皮肤干燥9例,腹泻3例,肝功能异常2例。结论 盐酸埃克替尼治疗EGFR突变阳性非小细胞肺癌脑转移疗效显著,临床应用前景光明。     

EML4-ALK融合介导EGFR-TKI耐药晚期肺腺癌个案报告

表皮生长因子受体（EGFR）基因突变和间变性淋巴瘤激酶（ALK）基因融合的发现显著改变了非小细胞肺癌的治疗模式，并使患者生存显著获益。ALK融合突变是EGFR酪氨酸激酶抑制剂（TKI）耐药的机制之一。我们报告了1例64岁晚期肺腺癌女性患者，其存在EGFR突变，并在EGFR-TKI耐药后发生了ALK融合，通过先后使用EGFR-TKI或ALK-TKI获得了长期生存，为ALK融合介导的EGFR-TKI耐药患者的靶向治疗药物选择提供参考。     

埃克替尼联合化疗治疗肺癌EGFR基因L833V和H835L罕见复合突变1例

非小细胞肺癌发生发展最常见的驱动因素是表皮生长因子受体（EGFR）突变,主要为19外显子缺失和第21外显子L858R突变,其他罕见基因突变发生率低,临床治疗方案尚未明确。本文报道1例携带EGFR基因H835L和L833V罕见突变的非小细胞肺癌患者,给予埃克替尼单药治疗3个月,疾病稳定（SD）,再予以埃克替尼联合化疗后病灶缩小,并维持SD近5个月。     

非小细胞肺癌患者外周血中EGFR基因突变与埃克替尼治疗效果的相关性

目的 探讨非小细胞肺癌（NSCLC）患者外周血液中表皮生长因子受体（EGFR）基因突变与埃克替尼治疗效果的相关性。方法 选取洛阳市第三人民医院自2014年2月-2018年2月收治的101例NSCLC患者作为实验对象,采用RT-PCR技术检测外周血液中EGFR基因突变情况,依据测定结果分为基因突变组和野生型组,均采用埃克替尼治疗分析其治疗效果;选取同期做健康体检的患者50例作为对照组,比较NSCLC患者与健康人外周血液中EGFR突变差异。结果 50例健康人外周血液检测EGFR基因突变率为0,NSCLC患者中EGFR基因突变率为41.58%（42例）,EGFR野生型组患者31.68%（32例）,EGFR基因未突变者27例。基因突变组患者疾病控制率为85.71%,治疗有效率为64.29%;野生型组疾病控制率为59.38%,总有效率仅为12.5%,数据差异有统计学意义（P<0.05）。随访6个月内两组患者生存率差异无统计学意义,随访1、2年间EGFR基因突变组的生存率均远高于野生型组,数据差异有统计学意义（P<0.05）。结论 NSCLC患者外周血中EGFR基因突变患者行埃克替尼治疗效果更高,因此在晚期的NSCLC患者治疗中可以通过测定是否EGFR基因突变来指导靶向药物治疗。     

醋酸阿比特龙联合多西他赛与泼尼松在转移性去势抵抗性前列腺癌患者中的应用及Naa10与治疗敏感性的关系

目的 探讨醋酸阿比特龙联合多西他赛与泼尼松在转移性去势抵抗性前列腺癌（mCRPC）患者中的应用及N-末端α位乙酰基转移酶基因10（acetyltransferase gene 10,Naa10）与治疗敏感性的关系。方法 回顾性选择2017年10月-2019年12月邢台医学高等专科学校第二附属医院收治的122例mCRPC患者为研究对象,入选患者均经过雄激素剥夺治疗。根据治疗方案不同将患者分为对照组和试验组,对照组患者静脉滴注多西他赛注射液,剂量75 mg·m^-2,每3周1次;口服醋酸泼尼松片,1次1片,每天2次;在注射多西他赛注射液化疗前1天、当天和后1天均口服醋酸地塞米松片,1日2次,总剂量7.5 mg。试验组患者在对照组的基础上空腹口服醋酸阿比特龙片,每次1 g,每日1次,治疗4个周期（12周）。比较两组患者近期临床疗效、不良反应及远期生存率等情况,随访3年,计算患者的中位生存期。免疫组化法检测mCRPC癌组织中Naa10蛋白表达,将患者分成Naa10阳性表达组和阴性表达组,分析其临床病理参数,单因素和Cox回归分析确定影响mCRPC预后的因素,分析Naa10蛋白阳性表达与治疗敏感性的关系。结果 治疗4个周期后,试验组患者9例完全缓解、40例部分缓解、8例疾病稳定及4例疾病进展,治疗总有效率为80.33%;对照组患者2例完全缓解、34例部分缓解、20例疾病稳定及5例疾病进展,治疗总有效率为59.02%,两组间比较差异显著（χ²=6.556,P=0.011）。试验组和对照组患者均出现骨髓抑制（χ²=0.209,P=0.648）、肝功能损伤（χ²=0.830,P=0.362）、胃肠道反应（χ²=0.370,P=0.543）、水钠潴留（χ²=0.209,P=0.648）及心脏毒性（χ²=0.899,P=0.343）等3级以上不良反应,但两组间差异未见显著性。mCRPC癌组织中Naa10蛋白阳性表达与治疗周期（χ²=9.106,P=0.003）、淋巴结转移（χ²=5.055,P=0.025）、T分期（χ²=4.391,P=0.036）、骨转移病灶数（χ²=19.863,P=0.000）、内脏转移（χ²=5.009,P=0.025）等具有显著相关性,但与年龄（χ²=3.059,P=0.080）、化疗方案（χ²=0.880,P=0.348）、EOCG评分（χ²=3.453,P=0.178）、民族（χ²=0.135,P=0.713）及Gleason评分（χ²=0.837,P=0.360）等没有显著相关性。单因素分析结果显示,mCRPC患者中位生存期与EOCG评分（χ²=7.464,P=0.006）、淋巴结转移（χ²=6.114,P=0.013）、化疗方案（χ²=7.049,P=0.030）、治疗周期（χ²=5.051,P=0.038）、T分期（χ²=1.196,P=0.035）、骨转移病灶数（χ²=9.611,P=0.008）、内脏转移（χ²=1.085,P=0.048）及Naa10蛋白阳性表达（χ²=15.600,P=0.000）等指标具有显著相关性。Cox回归分析结果显示,骨转移病灶数（>10个）（OR=2.404,95% CI：1.424~4.056）、治疗周期（>8个疗程）（OR=0.458,95% CI：0.253~0.832）、化疗方案（试验组）（OR=0.360,95% CI：0.160~0.801）和Naa10蛋白阳性表达（OR=2.563,95% CI：2.106~3.117）是mCRPC患者预后生存的独立影响因素（P<0.05）。结论 醋酸阿比特龙联合多西他赛与泼尼松应用于mCRPC治疗,可有效提高近期临床疗效,延长生存期,且不增加不良反应,同时Naa10蛋白高表达是mCRPC患者预后不良的危险因素,临床宜监测指标,及时调整和评估临床治疗效果。     

纳武利尤单抗联合安罗替尼治疗晚期非小细胞肺癌的临床研究

目的 探究纳武利尤单抗注射液联合盐酸安罗替尼胶囊治疗晚期非小细胞肺癌的临床疗效。方法 选取2019年1月—2020年1月临汾市中心医院收治的60例晚期非小细胞肺癌患者为研究对象,根据患者治疗方法不同分为对照组（29例）和治疗组（31例）。对照组患者早餐前口服盐酸安罗替尼胶囊,12 mg/次,1次/d,连续服药2周,停药1周。治疗组患者在对照组治疗的基础上静脉输注纳武利尤单抗注射液,3 mg/kg,1次/2周,评估患者耐受性和疗效。两组患者均持续治疗9周。观察两组近期临床疗效,比较治疗前后两组生活质量、T淋巴细胞亚群、血管内皮细胞生长因子（VEGF）水平变化和生存情况。结果 治疗后,治疗组客观缓解率（ORR）、疾病控制率（DCR）均较高于对照组,组间比较差异具有显著差异（P<0.05）。治疗后,两组患者CD3⁺、CD4⁺、CD4⁺/CD8⁺均明显升高,CD8⁺、VEGF均明显降低（P<0.05）;治疗组CD3⁺、CD4⁺、CD4⁺/CD8⁺均明显高于对照组,CD8⁺、VEGF均明显低于对照组（P<0.05）。治疗后2、4、6个月,两组EORTC QLQ-C30总评分均明显降低（P<0.05）,且治疗组EORTC QLQ-C30总评分明显低于同期对照组（P<0.05）。治疗后,治疗组中位无进展生存期（PFS）、总生存期（OS）较对照组明显增长（P<0.05）。结论 纳武利尤单抗注射液联合盐酸安罗替尼胶囊治疗晚期非小细胞肺癌具有较好的临床疗效,可改善患者的生活质量,调节患者免疫功能,降低VEGF水平,且不增加不良反应。     

艾迪注射液联合埃克替尼治疗非小细胞肺癌的临床研究

目的 研究艾迪注射液联合埃克替尼治疗非小细胞肺癌的效果。方法 选择2015年6月-2018年6月榆林市第一医院收治的84例非小细胞肺癌患者随机分为两组,每组42例。对照组采用盐酸埃克替尼片,观察组采用盐酸埃克替尼片联合艾迪注射液治疗,50 mL/次,1次/d。1个疗程为3周,均治疗3个疗程。比较两组的生活质量改善率、T细胞亚群水平和不良反应情况。结果 治疗后,观察组的有效率为69.05%,显著高于对照组的45.24%（P<0.05）。治疗后,观察组的生活质量改善率为61.90%,显著高于对照组的33.33%（P<0.05）。治疗后,观察组的CD8⁺、CD4⁺、CD3⁺和CD4⁺/CD8⁺水平均明显高于治疗前和对照组,差异均有统计学意义（P<0.05）;对照组治疗前后比较差异无统计学意义。观察组白细胞下降、恶心呕吐、血小板下降的发生率明显低于对照组（P<0.05）,两组肝、肾功能异常率相比无明显的差异。结论 艾迪注射液联合埃克替尼对非小细胞肺癌的效果较佳,能改善其CD细胞亚群水平和生活质量,减轻不良反应。     

Antitumor activity of aumolertinib,a third-generation EGFR tyrosine kinase inhibitor,in non-small-cell lung cancer harboring uncommon EGFR mutations

Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%–20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.     

Targeting epidermal growth factor receptor: Central signaling kinase in lung cancer

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Platinum-based doublets remain the current standard therapy for advanced NSCLC. However, overall survival (OS) has reached a plateau, even with the improvement in these regimens. Advances in the knowledge of molecular mechanisms of carcinogenesis have prompted the development of many novel molecular-targeted agents including the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Results of the recent phase III IPASS trial showed that the EGFR-TKI gefitinib has a superior progression-free survival (PFS) to the most commonly used platinum-based doublet carboplatin-paclitaxel as the first-line chemotherapy for pulmonary lung adenocarcinoma among nonsmokers in East Asia. This trial also demonstrated that the presence of EGFR mutation is the best predictor of gefitinib treatment compared with the other biomarkers including EGFR gene copy number. Despite the therapeutic benefit of EGFR-TKIs in NSCLC, most patients eventually develop resistance to these drugs. A secondary mutation of EGFR (T790M) and amplification of MET account for 70% of all cases of acquired resistance to EGFR-TKIs. This review summarizes the significance of EGFR mutations and the mechanisms of resistance to EGFR-TKIs in NSCLC, both of which are critical for patient selection to extend survival as well as to overcome resistance in NSCLC patients treated with EGFR-TKIs.     

Protein kinase inhibitors to treat non-small-cell lung cancer

Introduction: Activating mutations of the EGFR and rearrangement of anaplastic lymphoma kinase (ALK) best illustrate the therapeutic relevance of molecular characterization in NSCLC patients.

Areas covered: For this review article, all published data on the most relevant Phase III trials with tyrosine kinase inhibitors (TKIs) for the treatment of NSCLC were collected and analyzed.

Expert opinion: Eight Phase III trials clearly established EGFR TKIs as the best therapeutic option for front-line therapy in EGFR-mutated patients. In pretreated NSCLC, EGFR TKIs are considered more effective than standard monotherapy with cytotoxics in presence of classical EGFR mutations, whereas in the EGFR wild-type population, a similar efficacy to docetaxel or pemetrexed in term of survival has been demonstrated. In ALK-translocated NSCLC, a Phase III trial demonstrated the superiority of a multi-target TKI, including ALK, in terms of progression-free survival, response rate and toxicity profile when compared to standard second-line chemotherapy. New agents targeting EGFR or ALK are under evaluation particularly in individuals with acquired resistance to EGFR TKIs or crizotinib.     

Pharmacokinetic drug evaluation of osimertinib for the treatment of non-small cell lung cancer

Introduction: First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9–13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice.

Areas covered: A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken.

Expert opinion: Osimertinib is the standard-of-care for EGFR-mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR-mutated NSCLC patients will change further in the next few years.     

Pharmacotherapy targeting the EGFR oncogene in NSCLC

Introduction: The EGFR plays a central role in regulating cancer cell growth and survival, representing an attractive therapeutic target in NSCLC.

Areas covered: For the purpose of this review article, data from Phase II and III trials with anti-EGFR agents, including EGFR-tyrosine kinase inhibitors (TKIs) and mAbs, were collected and analysed.

Expert opinion: Eight large Phase III trials demonstrated that EGFR-TKIs are the best option we can offer today as front-line therapy exclusively in EGFR mutant NSCLC. In patients with EGFR wild type or unknown lung cancer, platinum-based chemotherapy remains the standard of care, with no consistent benefit produced by the addition of an anti-EGFR treatment. In pretreated NSCLC, EGFR-TKIs are considered more effective than standard monotherapy with cytotoxics in presence of classical EGFR mutations, whereas in the EGFR wild-type population, a similar efficacy with docetaxel or pemetrexed in terms of survival has been demonstrated. New agents targeting EGFR are under investigation, particularly in individuals with squamous cell histology and those with acquired resistance to EGFR-TKIs.     

Osimertinib for EGFR T790M mutation-positive non-small cell lung cancer

Introduction: Significant advances have been made since the development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR mutations in non-small-cell lung cancer (NSCLC), however, lung cancer cells eventually acquire resistance to those agents. Osimertinib (AZD9291) has been developed as 3^rd generation EGFR-TKI with activities against sensitizing mutations and T790 M resistance mutation, which account for about 50% of the mechanisms of acquired resistance to 1^st or 2^nd generation EGFR-TKIs. A recent phase I/II clinical trial with osimertinib for advanced NSCLC patients with known sensitizing EGFR mutations and documented disease progression on prior EGFR-TKIs revealed promising effect with acceptable toxicities.

Areas covered: This article summarizes current understanding and available preclinical and clinical data on osimertinib and also discusses future directions. The literature search included PubMed and the latest articles from international conferences.

Expert commentary: The development of osimertinib has provided new therapeutic options for NSCLC patients harboring T790 M. Compared with other EGFR-TKIs including rociletinib, osimertinib seems to possess an advantage with respect to the effect and safety profile among existing EGFR-TKIs. However, tumor progression still occurs even when treating with osimertinib. A further understanding of the mechanisms of resistance is eagerly anticipated in order to develop next generation EGFR-TKIs.     

Impact of a multivariate serum-based proteomic test on physician treatment recommendations for advanced non-small-cell lung cancer

Objective: The VeriStrat¹ (VS) test is intended to help guide treatment decisions for patients with advanced non-small-cell lung cancer (NSCLC) without an EGFR-sensitizing mutation, classifying patients into two categories. Patients classified as VSGood have a favorable prognosis and significant clinical response to EGFR tyrosine kinase inhibitors (TKIs). Patients classified as VSPoor have a less favorable prognosis and exhibit no significant response to EGFR-TKIs. The objective of this paper is to assess the real-world impact of VS test results on physicians’ treatment recommendations including referrals for best supportive care (BSC).

Methods: Between 1 January 2012 and 1 November 2016, physician respondents were asked to complete standardized questionnaires before and after receiving VS results in patients meeting criteria for the intended use of the VS test. This study evaluated three endpoints: whether physicians followed VS test results in making treatment recommendations, the extent to which tests results changed these treatment recommendations, and the patterns of care subsequent to VS testing.

Results: Of the tests ordered by 989 physicians, 2494 VS tests had completed treatment recommendation questionnaires both prior to and after testing. Prior to VS testing, physicians were considering treatment with EGFR-TKIs for 2250 patients (90%). The VS test classified 1950 patients as VSGood and 544 patients as VSPoor. For patients classified as VSPoor, physicians recommended BSC for 25% of patients and standard systemic treatments such as chemotherapies for 65% of patients. Consistent with previous publications, physicians recommended EGFR-TKI therapy for only 10% of VSPoor patients but for 89% of VSGood patients. Overall, physician’s treatment recommendations were consistent with test results in 98% of cases. Availability of test results decreased ineffective treatment recommendations by 89% for VSPoor patients.

Conclusions: Among physicians ordering VS, the test significantly influenced treatment recommendations for patients with NSCLC, reducing ineffective and expensive treatment at the end of life.     

Recent understanding of the molecular mechanisms for the efficacy and resistance of EGF receptor-specific tyrosine kinase inhibitors in non-small cell lung cancer

Introduction: The epidermal growth factor receptor (EGFR) and its family members are involved in many aspects of tumor biological processes. Aberrant activation of the EGFR tyrosine kinase by mutations or protein overexpression is observed in various types of human cancer, including lung cancer. EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, are highly effective in lung cancer patients who harbor active mutations in the EGFR gene. However, patients who are initially sensitive to EGFR-TKIs eventually relapse within few years.

Areas covered: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and is associated with a high frequency of EGFR mutations. This review describes the EGFR mutations that determine the sensitivity to EGFR-TKIs and the current understanding of the molecular mechanisms of acquired resistance to EGFR-TKIs in NSCLC. Furthermore, the authors describe recent strategies developed to overcome acquired resistance using second-generation EGFR-TKIs and combination therapies with several molecular-targeting drugs.

Expert opinion: Although recent findings have contributed to our understanding of the mechanism of acquired resistance and helped the development of novel strategies to overcome such resistance, the underlying mechanisms are complex and additional research is necessary to develop effective therapeutic strategies for individual patients with lung cancer.