PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Strategies to overcome resistance to epidermal growth factor receptor monoclonal antibody therapy in metastatic colorectal cancer

Administration of monoclonal antibodies(mAbs)against epidermal growth factor receptor(EGFR)such as cetuximab and panitumumab in combination with conventional chemotherapy substantially prolongs survival of patients with metastatic colorectal cancer(mCRC).However,the efficacy of these mAbs is limited due to genetic variation among patients,in particular K-ras mutations.The discovery of K-ras mutation as a predictor of non-responsiveness to EGFR mAb therapy has caused a major change in the treatment of mCRC.Drugs that inhibit transformation caused by oncogenic alterations of Ras and its downstream components such as BRAF,MEK and AKT seem to be promising cancer therapeutics as single agents or when given with EGFR inhibitors.Although multiple therapeutic strategies to overcome EGFR mAb-resistance are under investigation,our understanding of their mode of action is limited.Rational drug development based on stringent preclinical data,biomarker validation,and proper selection of patients is of paramount importance in the treatment of mCRC.In this review,we will discuss diverse approaches to overcome the problem of resistance to existing anti-EGFR therapies and potential future directions for cancer therapies related to the mutational status of genes associated with EGFRRas-ERK and PI3K signalings.

Dual Epidermal Growth Factor Inhibition and Multi Targeted Epigenetic Therapy (MTET)

Since the discovery of tyrosine kinase inhibitors in treatment of lung cancer harboring such actionable targets, many lives have been prolonged. To the same extent, same group of patients have failed to benefit from this category of drugs, in long run, either initially or during the course of treatments, simply due to either known or unknown mechanism of resistance which occurs very often in the first few months after initiation of therapy. The resistance is 100 percent expected, and no patient is reported to be a waiver of such pattern. With best practices of oncology, the average duration of response is expected to be below 12 months [1]. About half of the resistance is caused by mutation at T790M in EGFR target, which can be revealed by liquid biopsy [1] [2]. The most recent studies have revealed the significant role of epigenome in controlling this complicated resistance pattern. We have learned that Histone deacetylation, as opposed to promoter methylation, may contribute to the epigenetic silencing and to EGFR TKI resistance in NSCLC [3] [4]. Here we present a case study with a model of combinational therapy that targets the EGFR molecule, (by small molecule inhibitor, Afatanib) with simultaneous epigenetic modification of the target, (by application of multitargeted epigenetic therapy (MTET) with significantly improved clinical results. We propose further trials are needed to support such hypothesis, which if proved, could significantly shift the current practices in management of this set of cases in lung adenocarcinomas.

Effects of epidermal growth factor on sperm content and motility of rats with surgically induced varicoceles

Aim： To investigate the effect of epidermal growth factor （EGF） on the sperm content and motility of the varicocelized rats. Methods： Forty-eight male Wistar rats were randomly divided into five groups. Experimental varicocele was induced by partial ligation of the left renal vein in the varicocele, the varicocele repair, the varicocele with EGF and the varicocele repair with EGF groups, whereas the control group only received a sham induction of varicocele. Surgical repair of varicocele was performed 4 months later in the varicocele repair and varicocele repair with EGF groups. EGF administration was performed daily by s.c. injection in the varicocele with EGF and varicocele repair with EGF groups at the dose of 10 μg/（kg·day） from the next day of the second surgery. One month later, all animals were killed and bilateral cauda epididymal sperm counts and motility were evaluated. Results： The mean sperm count and percentage of motile spermatozoa were significantly higher bilaterally in the varicocele with EGF group than in the varicocele group （P 〈 0.05）. They were also significantly higher bilaterally in the varicocele repair with EGF group than in the varicocele repair and the varicocele with EGF groups （P 〈 0.05）. Conclusion： EGF can improve bilateral epididymal sperm content and motility of the rat with surgically induced varicocele. The administration of EGF in combination with surgical repair is more effective than surgical repair or EGF administration alone. EGF might be useful for the treatment of infertility induced by varicocele.

Correlation of human epidermal growth factor receptor protein expression and colorectal cancer

AIM:To investigate the correlation between human epidermal growth factor receptor(HER-2) protein expression and colorectal cancer(CRC) using a casecontrol study and meta-analysis.METHODS:Tumor tissue specimens from 162 CRC patients were selected for the case group.Fifty cases were randomly selected,and normal CRC tissue at least 10 cm away from the tumor margins of these cases was used to generate the control group.The expression of the HER-2 protein in the 162 CRC tissue samples and the 50 adjacent normal mucosa tissue samples was detected via immunohistochemistry.The experimental data were analyzed using SPSS 18.0software,and R software version 3.1.0 was utilized for further verification.RESULTS:The expression of HER-2 protein in the 162 CRC tissue samples was significantly higher than in the normal tissue specimens.The data showed that the expression of HER-2 in CRC was related to the Dukes' stage,the depth of invasion and lymph node metastasis.The HER-2-positive patients had lower 3-and 5-year OS rates than the HER-2-negative patients,but there was no significant difference.However,there was a statistically significant difference in the 3- and5-year disease-free survival(DFS) rates of HER-2-positive and HER-2-negative patients.The results of the meta-analysis showed that the expression of HER-2in CRC patients was statistically significantly increased over that of healthy people.The 3-year DFS rate in HER-2-positive patients was markedly lower than that in HER-2-negative patients.CONCLUSION:Down-regulation of HER-2 expression might be a dependable strategy for CRC therapy.

Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.

Research Progress in Targeted Therapy for Esophageal Cancer

Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal cancer (EC) patients at advanced or metastatic stages. While historically considered incurable, ongoing advancements in medical research have led to the integration of various treatment modalities as primary approaches for managing advanced endometrial cancer. These modalities include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Notably, the introduction of targeted therapy and immunotherapy has significantly enhanced the survival rates of individuals with EC. Immunotherapy has appeared as the predominant treatment for advanced esophageal cancer, while targeted therapy faces certain obstacles. Consequently, this review primarily focuses on the advancements in targeted therapy for esophageal cancer (EC), evaluating the effectiveness and safety of relevant medications, and aiming to provide guidance for the comprehensive management of EC based on current research findings.

Epidermal growth factor receptor compound and concomitant mutations:advances in precision treatment strategies

Epidermal growth factor receptor(EGFR)mutations are common oncogenic driver mutations in patients with non-small cell lung cancer(NSCLC).The application of EGFR-tyrosine kinase inhibitors(TKIs)is beneficial for patients with advanced and early-stage NSCLC.With the development of next-generation sequencing technology,numerous patients have been found to have more than one genetic mutation in addition to a single EGFR mutation;however,the efficacy of conventional EGFR-TKIs and the optimal treatments for such patients remain largely unknown.Thus,we review the incidence,prognosis,and current treatment regimens of EGFR compound mutations and EGFR concomitant mutations to provide treatment recommendations and guidance for patients with these mutations.

双靶向新辅助药物联合不同化疗治疗HER-2阳性乳腺癌临床疗效比较

目的探讨双靶向新辅助药物联合不同化学药物治疗(简称化疗)的方案治疗人类表皮生长因子受体-2(HER-2)阳性乳腺癌的临床疗效。方法选取凉山彝族自治州第一人民医院2019年1月至2022年12月收治的HER-2阳性乳腺癌患者110例,按治疗方案的不同分为TcbHP组和AC-THP组,各55例。TcbHP组患者予曲妥珠单抗和帕妥珠单抗联合紫杉类(多西他赛或紫杉醇)和卡铂治疗,以21 d为1个周期,共治疗6个周期;AC-THP组患者予曲妥珠单抗和帕妥珠单抗联合蒽环类药物(吡柔比星或表柔比星)和环磷酰胺治疗,以21 d为1个周期,曲妥珠单抗和帕妥珠单抗及其他药物分别治疗4个周期,共8个周期。结果TcbHP组患者病理完全缓解率为61.80%,稍高于AC-THP组的50.90%(P>0.05)。治疗后,TcbHP组恶心,呕吐,腹泻,心脏毒性及手足综合征程度均显著低于AC-THP组(P<0.05);各肿瘤标志物[糖类抗原(CA19-9,CA125,CA153),癌胚抗原(CEA)]水平均显著低于AC-THP组(P<0.05);左心室射血分数(LVEF)及血清心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶MB(CK-MB)、氨基末端脑钠肽前体(NT-proBNP)水平均无明显变化(P>0.05),且均显著优于AC-THP组(P<0.05)。结论TcbHP方案治疗HER-2阳性乳腺癌的疗效与AC-THP方案相当,但前者降低肿瘤标志物生成的作用更明显,且心脏毒性风险相对更低。

Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer

Background The genotype of epidermal growth factor receptor （EGFR） is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer （NSCLC）. In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis. Methods We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes. Results There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients （37.0% vs. 31.9%）. The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types （24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P=0.047）. Clinical stage （Ⅳvs. Ⅲb）, response to the first-line chemotherapy （partial vs. no） and EGFR genotype were independent prognostic factors. Conclusion Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.

Cost-effectiveness analysis of tyrosine kinase inhibitors(erlotinib,gefitinib,afatinib and osimertinib)as first-line therapy for epidermal growth factor receptor-mutated advanced non-small cell lung cancer

Gefitinib,erlotinib,afatinib and osimertinib have been recommended as the first-line treatment for epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC),whereas no studies have compared the cost-effectiveness of these four tyrosine kinase inhibitors(TKIs)simultaneously in China.In the present study,we aimed to estimate the cost-effectiveness of erlotinib,gefitinib,afatinib and osimertinib for untreated EGFR-mutated advanced NSCLC.A Markov model was constructed to compare the 10-year impact of four TKIs for patients with treatment-naive EGFR-mutated advanced NSCLC from the perspective of the Chinese medical system.Clinical data and utility values were derived from published literature,and costs were obtained from Chinese official websites.The primary output indicator was the incremental cost-effectiveness ratio(ICER).Sensitivity analyses were performed to test the robustness of the model.We found that afatinib was estimated to spend the lowest cost with minimum life-years(LYs),while osimertinib was the most expensive regimen with maximum LYs.The ICER of gefitinib versus afatinib was$732/quality-adjusted life-year(QALY),which was less than the willingness-to-pay(WTP)of$29382/QALY.Compared with gefitinib,erlotinib yielded a higher cost and a shorter lifetime,hence it was identified as a dominated strategy.Then,osimertinib was compared to gefitinib,which produced an ICER of$71330/QALY,exceeding the WTP.It suggested that gefitinib was the most cost-effective regimen as the first-line treatment for EGFR-mutated advanced NSCLC.Decreasing the osimertinib price or increasing the WTP threshold to$68558/QALY might enhance the favorability of the outcome,by which osimertinib might become more cost-effective.One-way sensitivity analysis manifested that the model was robust.

THP方案新辅助治疗HER-2阳性乳腺癌的真实世界研究

目的 了解THP方案在真实世界临床实践的应用状况,同时评价该方案的疗效、安全性和耐受性。方法 选择在保定市第一中心医院等河北省11家三级甲等医院接受THP方案新辅助治疗并完成序贯手术的HER-2阳性乳腺癌患者70例为研究对象,制订专用的患者资料信息收集表,专人负责收集符合纳入标准患者的临床病理资料。评估THP方案的有效性、安全性和耐受性。主要研究终点为病理完全缓解(pCR)率、≥3级不良反应的发生率、既定治疗方案完成率。结果 总人群pCR率为54.3%。亚组分析显示,cTNMⅠ-Ⅱ期、激素受体阴性、HER-2 IHC3+患者的pCR率分别显示出高于c TNMⅢ期、激素受体阳性、HER-2 IHC2+/FISH+患者的趋势,但差异无统计学意义(P>0.05)。4周期患者的pCR率显著高于4周期以上患者(P<0.05)。≥3级不良反应发生率为4.3%。既定方案完成率为98.6%。结论THP方案在河北省得到广泛应用,是HER-2阳性乳腺癌患者新辅助治疗的有效方案,安全性及耐受性良好,可以考虑作为激素受体阴性、肿瘤负荷较小、对联合化疗耐受性差患者的新辅助备选方案。

MRI及临床病理特征对乳腺癌人表皮生长因子受体2表达状态的鉴别诊断价值

目的 探讨MRI联合临床病理特征在乳腺癌人表皮生长因子受体2(human epidermal growth factor receptor 2, HER-2表达状态中的鉴别诊断价值,尤其是在HER-2低表达乳腺癌中的鉴别诊断价值。材料与方法 回顾性分析2018年1月至2019年12月在复旦大学附属肿瘤医院经病理证实为乳腺癌的患者治疗前乳腺MRI图像,205例患者均行双侧乳腺平扫及增强MRI检查。根据免疫组织化学和荧光原位杂交结果将HER-2状态分为HER-2阴性(包括零、低表达)和阳性(过表达)。分析各组临床病理特征及MRI特征,临床病理特征包括年龄、月经状态、雌激素受体(estrogen receptor, ER)、孕激素受体(progesterone receptor, PR)、激素受体(hormone receptor, HR)、分子分型和Ki-67水平。MRI特征包括纤维腺体类型、背景实质强化、多灶或多中心、瘤内T2WI高信号、瘤周水肿、病灶类型、病灶大小、肿块形状、边缘、内部强化模式、非肿块强化分布及内部强化模式。单因素分析中,对于HER-2阴、阳性组间比较,年龄采用独立样本t检验,病灶大小采用Mann-Whitney U检验,其余临床病理特征及MRI特征采用χ^(2)检验;对于HER-2零、低和过表达组的比较,年龄采用单因素方差分析,病灶大小采用Kruskal-Wallis H检验;其余临床病理特征及MRI特征采用χ^(2)检验。多因素分析采用二元logistic回归分析,用受试者工作特征曲线下面积(area under the curve, AUC)、敏感度和特异度评价模型的诊断效能。结果 HER-2阴性中零表达59例、低表达79例,HER-2阳性(过表达) 67例。HER-2阴性与阳性组临床病理特征中,ER、PR、HR和分子分型差异有统计学意义(P均<0.001),MRI特征中肿块边缘差异有统计学意义(P=0.020)。进一步比较HER-2低表达组与零表达组、HER-2低表达组与过表达组,临床病理特征中,ER、PR、HR、分子分型和Ki-67水平(以中位数40%为截断值)组间差异具有统计学意义(ER、PR、HR、分子分型:P均<0.001;Ki-67:P<0.001,P=0.037);MRI特征中,瘤内T2WI高信号与肿块形状组间差异具有统计学意义(瘤内T2WI高信号:P=0.031,P=0.011;肿块形状:P=0.012,P=0.025),且肿块边缘在HER-2低表达与零表达组间差异有统计学意义(P=0.036)。联合临床病理和MRI特征的多因素分析提示,PR状态、Ki-67水平及肿块形状是鉴别乳腺癌HER-2低表达与零表达的独立预测因素,AUC、敏感度和特异度分别为0.772、79.7%和70.9%;PR状态及瘤内T2高信号是鉴别HER-2低表达与过表达的独立预测因素,AUC、敏感度、特异度分别为0.793、69.8%和76.1%。结论 MRI影像特征对乳腺癌HER-2表达状态具有鉴别诊断价值,尤其在HER-2低表达与零表达或过表达乳腺癌鉴别诊断中。联合临床病理特征,PR阳性、Ki-67低于40%、肿块形状不规则和瘤内T2WI高信号可提示HER-2低表达乳腺癌。

肺癌分子靶向治疗EGFR-TKI患者证候及中医处方用药研究进展

表皮生长因子受体酪氨酸激酶抑制剂(Epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI)是肺癌治疗领域的里程碑,中医药与分子靶向治疗EGFR-TKI相结合是肺癌综合治疗的新模式。辨证论治是中医的特色,中医药的精准配合,可以贯穿于分子靶向治疗EGFR-TKI的全程。通过查阅、归纳及分析近年来不同专家学者对分子靶向治疗EGFR-TKI相关肺癌患者不同治疗阶段的中医证候及中医处方用药研究的文献,总结肺癌分子靶向治疗EGFR-TKI患者在不同治疗阶段的证候分布及中医处方用药特点,促使中医辨证论治更加精准,旨在进一步提高临床上中医药配合分子靶向治疗EGFR-TKI的效果。

G719X/L861Q/S768I突变非小细胞肺癌诊断及靶向治疗进展

肺癌在全球癌症死亡原因中占比最高,对人类健康造成了极大威胁。30%-40%的非小细胞肺癌(non-small cell lung cancer,NSCLC)的发生是由于表皮生长因子受体(epidermal growth factor receptor,EGFR)发生点突变、外显子插入、外显子缺失导致。除常见的19号外显子缺失突变和21号外显子L858R突变外,18号外显子G719X突变、21号外显子L861Q突变、20号外显子S768I突变是最主要的罕见突变。目前,针对主要罕见突变的诊断方法主要是下一代测序技术(next-generation sequencing,NGS)、数字聚合酶链式反应(digital polymerase chain reaction,dPCR)、微滴式数字PCR(droplet digital PCR,ddPCR)等。关于G719X/L861Q/S768I突变NSCLC的靶向治疗,第一代EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)疗效较差,第二代和第三代EGFR-TKIs疗效相当,新型第三代EGFR-TKIs和联合治疗展现出不错的治疗前景。本文对G719X/L861Q/S768I突变NSCLC诊断及靶向治疗进展进行了归纳,以期为后续临床用药及研究提供参考。

EGFR外显子20插入突变:研究现状与治疗新策略

作为非小细胞肺癌(non-small cell lung cancer,NSCLC)中重要的致癌驱动基因,表皮生长因子受体外显子20插入突变(epidermal growth factor receptor exon 20 insertion,EGFR ex20ins)具有独特蛋白构象,并且对传统EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)原发耐药。近年来,靶向EGFR ex20ins的药物探索从未停止。莫博赛替尼与埃万妥单抗率先被美国食品药品监督管理局(Food and Drug Administration,FDA)获批用于EGFR ex20ins突变NSCLC患者,随后舒沃替尼等药物取得突破,联合治疗方案的探索也有所收获。多管齐下有望克服EGFR ex20ins耐药。因此,深入了解EGFR ex20ins的分子机制并评估新型药物的有效性与差异性至关重要。本文将对相关最新研究成果进行全面总结,以期为EGFR ex20ins突变患者精准治疗提供有价值的参考。

HR+/HER2-乳腺癌与HR+/HER2+乳腺癌临床特征和内分泌治疗时长的比较

目的比较免疫组化激素受体阳性、人表皮生长因子阴性(HR+/HER2-)乳腺癌患者和激素受体阳性、人表皮生长因子受体阳性(HR+/HER2+)乳腺癌患者的临床特征和内分泌治疗时长。方法回顾性分析青岛大学附属医院收治的36例HR+/HER2-乳腺癌患者和22例HR+/HER2+乳腺癌患者的临床资料,比较两组患者的年龄、月经状态、骨转移、肺转移、肝转移、淋巴结转移、总转移数、BMI、BI-RADS分级、ECOG评分,以及总线数、一线、二线、三线及以上内分泌治疗时长。结果两组患者年龄、月经状态、肺转移、肝转移、淋巴结转移、总转移数、BMI、BI-RADS分级、ECOG评分,以及总线数、一线、二线、三线及以上内分泌治疗时长比较,差异均无统计学意义(P>0.05);HR+/HER2+组患者骨转移发生率高于HR+/HER2-组(P<0.05),HR+/HER2-组患者三线及以上内分泌治疗时长长于HR+/HER2+组(P<0.05)。结论HR+/HER2+乳腺癌可积极选用内分泌治疗或与HER2靶向药物联合治疗,从而避免使用化疗,减轻化疗所带来的不良反应。

分子靶向治疗在EGFR突变肺鳞癌中的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)是我国常见的肿瘤之一,肺鳞癌是NSCLC中除肺腺癌外最常见的组织学亚型。表皮生长因子受体(epidermal growth factor receptor,EGFR)是肺癌的驱动基因之一,相比肺腺癌,肺鳞癌中EGFR的突变率很低。针对EGFR的靶向治疗在肺腺癌中已经取得了重大进展,而在肺鳞癌中的进展相对缓慢。本文对近年EGFR突变肺鳞癌分子靶向治疗的相关研究进行综述,总结出EGFR-酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)在肺鳞癌中的疗效,旨在为EGFR突变肺鳞癌患者的治疗提供参考。