厄洛替尼治疗晚期结肠癌1例报告

以表皮生长因子受体（epidermal growth factor receptor,EGFR）为靶点的小分子酪氨酸激酶抑制剂厄洛替尼主要用于晚期非小细胞肺癌的治疗,其在治疗晚期结直肠癌则少有报告。本科室采用厄洛替尼治疗了1例多线方案失败的晚期结肠癌患者取得了较好疗效,现报告如下。     

盐酸安罗替尼治疗晚期肺癌中国专家共识(2020版)

盐酸安罗替尼是目前国内唯一获批治疗晚期非小细胞肺癌(NSCLC)和晚期小细胞肺癌(SCLC)的抗血管生成多靶点小分子酪氨酸激酶抑制剂。为了更好地指导临床合理、有效、安全地使用盐酸安罗替尼治疗晚期肺癌, 给医师提供基于循证医学研究结果的用药建议和参考, 中国医师协会肿瘤医师分会、中国临床肿瘤学会血管靶向治疗专家委员会和中国抗癌协会肿瘤靶向治疗专业委员会共同组织专家, 整合了盐酸安罗替尼多项临床试验结果、临床应用的安全性数据以及专家临床实践经验, 共同制定了本共识。共识的内容覆盖盐酸安罗替尼在NSCLC和SCLC中的使用及安全性管理建议等。     

安罗替尼在晚期恶性肿瘤治疗中的研究进展

安罗替尼是我国自主研发的多靶点小分子酪氨酸激酶抑制剂,具有抗肿瘤血管生成和抑制肿瘤细胞生长的作用,因其具有不良反应小、靶点明确及安全性高等优点,目前已在多种恶性肿瘤中显示出了良好的临床疗效,本文就安罗替尼的抗肿瘤作用机制、其在多种类型肿瘤中的应用以及不良反应与管理等方面的最新研究进展进行综合阐述。     

克里唑替尼在非小细胞肺癌中的研究进展

肺癌中的一大部分为非小细胞肺癌(NSCLC)。克里唑替尼作为ALK和MET的酪氨酸激酶抑制剂,是一种小分子靶向ALK突变的治疗药物,可以通过抑制ALK突变而产生抗NSCLC的作用。克里唑替尼通过抑制NSCLC中ALK激酶与ATP的结合及结合后的自身磷酸化而抑制激酶的激活,进而降低激酶活性,起到抗肿瘤作用。克里唑替尼以其高有效率已经获得FDA批准进行III期临床试验,是目前最早也是唯一一个进行III期临床试验的ALK酪氨酸激酶抑制剂。大多数的不良反应如一过性视觉障碍、胃肠道反应、疲惫等多处于比较轻微的1-2级水平。耐药情况的出现严重限制了其临床应用,因此,对于其耐药机制的研究有助于尽早研制出二代ALK抑制剂,取得更好的临床疗效。目前ALK突变的3种主要检测方法为:Break-apart FISH,RT-PCR,免疫组织化学方法(IHC)。     

阿帕替尼联合曲妥珠单抗治疗晚期胃癌1例

胃癌是我国常见的恶性肿瘤. 2015年我国胃癌新发病例约67. 9万例,其死亡病例约49. 8万例,仅次于肺癌. 由于早期症状不典型,胃癌患者在确诊时常发生远处转移,而且生存较差,严重威胁人类的健康和生命[1]. 阿帕替尼( Ap-atinib)是新一代小分子酪氨酸激酶抑制剂,高度选择性地抑制VEGFR-2酪氨酸激酶活性,强效抑制肿瘤血管生成. 现将我院收治的1例接受阿帕替尼联合曲妥珠单抗治疗晚期胃癌的诊治过程报告如下.     

伊马替尼治疗胃肠道间质肿瘤研究进展

胃肠道间质肿瘤(gastrointestinal stroma tumor,GIST)病理发生学的重要因素是KIT受体酪氨酸的活性表达.伊马替尼是一种选择性酪氨酸激酶抑制剂,在临床前期及基础临床研究中,已显示出了抑制胃肠道间质肿瘤的活性.     

甲磺酸阿帕替尼治疗晚期非小细胞肺癌的研究现状

甲磺酸阿帕替尼,一种小分子酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI),作用于血管内皮生长因子受体-2(vascular endothelial growth factor receptor-2,VEGFR-2),强效抑制内皮细胞新生血管生成。阿帕替尼是在中国获得批准的第一代口服抗血管生成药物,用于晚期胃癌标准化疗失败的后续治疗。目前阿帕替尼单药或者联合其他治疗在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)中的临床研究正在积极开展,多数均显示一定生存获益。本文详细介绍近年阿帕替尼在晚期NSCLC中的研究现状,为后期临床应用提供参考。     

瑞派替尼治疗晚期胃肠间质瘤的研究进展

胃肠间质瘤是一类起源于胃肠道间叶组织的肿瘤，具有复杂的肿瘤异质性，酪氨酸激酶抑制剂是胃肠间质瘤全身治疗的基础药物，显著延长了晚期胃肠间质瘤患者的生存期，但由于肿瘤基因突变位点的继发性改变，使得传统酪氨酸激酶抑制剂在晚期胃肠间质瘤的治疗存在一定局限性。瑞派替尼是一种新型的酪氨酸激酶抑制剂，可以广谱抑制KIT和血小板源性生长因子受体α的突变，从而发挥抑制肿瘤增殖的作用，为晚期胃肠间质瘤患者提供了更多的治疗机会。全文根据瑞派替尼Ⅰ期、Ⅲ期临床试验进展以及最新指南研究，就瑞派替尼的作用机制、疗效和临床应用进行综述。     

埃罗替尼治疗吉非替尼耐药的晚期非小细胞肺癌有效1例

晚期非小细胞肺癌(NSCLC)预后差,以化疗为主的联合治疗只能降低死亡风险26%-32%[1].近年来,非小细胞肺癌的靶向治疗成为研究热点,其中尤以表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)进展最快,其代表药物吉非替尼(gefitinib、iressa)和埃罗替尼(erlotinib、tarceva).我科用埃罗替尼治疗吉非替尼耐药的晚期非小细胞肺癌(NSCLC)一例取得了较好疗效,现报告如下.     

埃罗替尼治疗吉非替尼耐药的晚期非小细胞肺癌有效1例

晚期非小细胞肺癌（NSCLC）预后差,以化疗为主的联合治疗只能降低死亡风险26％-32％。近年来,非小细胞肺癌的靶向治疗成为研究热点,其中尤以表皮生长因子受体酪氨酸激酶抑制剂（EGFR—TKI）进展最快,其代表药物吉非替尼（gefitinib、iressa）和埃罗替尼（erlotinib、tarceva）。我科用埃罗替尼治疗吉非替尼耐药的晚期非小细胞肺癌（NSCLC）一例取得了较好疗效,现报告如下。     

Tyrosine kinase inhibitors.

Tyrosine kinases are associated with the cytoplasmic domains of growth factor receptors as well as oncoproteins and many have the potential to cause transformation if mutated or hyperexpressed. Tyrosine kinases therefore represent an excellent target for the development of cancer drugs. A large number of inhibitors have now been identified and many show promising cytostatic activity, particularly using in vitro models. Some in vivo activity has been reported. Progress with various structural classes is reviewed. It is not clear whether specific or broad spectrum tyrosine kinase inhibitors should be developed as potential anticancer drugs. It does seem likely, however, that tyrosine inhibitors will enter clinical trial in cancer patients.     

Tyrosine kinase inhibitors in pediatric malignancies

Tyrosine kinase inhibitors have been used to treat adult cancers for over a decade. Since the discovery of imatinib mesylate (STI-571, Gleevec; Novartis), tyrosine kinase inhibitors have ushered in a new age of targeted therapy. Although the United States Food and Drug Administration has approved several kinase inhibitors for use in adult cancers, currently only imatinib mesylate is approved for use in children with cancer. This review highlights the mechanisms of tyrosine kinase inhibition, the potential role of tyrosine kinase pathways in the treatment of pediatric cancers, and the current status of pediatric clinical investigation of a spectrum of tyrosine kinase inhibitors for the treatment of childhood cancer.     

Tyrosinkinaseinhibitoren

Tyrosine kinase inhibitors are paradigms of molecularly targeted drugs in hematology/oncology. The first clinically introduced agent was imatinib (Glivec?). The feasibility of treatment with a small molecule was impressively demonstrated by treatment of chronic myeloid leukemia. This milestone of progress was followed by introduction of novel kinase inhibitors into clinical practice, which significantly impacted treatment options for leukemias and solid tumors such as renal cell carcinoma, lung cancer, hepatocellular carcinoma, or breast cancer. When prescribing tyrosine kinase inhibitors, specific mechanisms of action, class- and substance-specific side effects, compliance, development of resistance, potential for cure, and last but not least economic aspects need to be considered.     

Gastrointestinal stromal tumors: a spectrum of disease

The majority of gastrointestinal stromal tumors (GIST) express c-kit, a growth factor receptor with tyrosine kinase activity. Mutations in the c-kit proto-oncogene may lead to constitutive ligand-independent activation of c-kit and subsequent neoplastic transformation. Selective tyrosine kinase inhibitors target this property of GIST and have become the standard chemotherapy for metastatic or unresectable tumors. The mainstay of treatment, however, continues to be complete surgical resection. Tyrosine kinase inhibitors may prove expedient for adjuvant therapy, and are currently the focus of clinical trials conducted by the ACOSOG, RTOG, and ACRIN. It is important to distinguish GISTs from other mesenchymal tumors of the GI tract because of differences in natural history, as well as the efficacy of treatments targeting the GIST tyrosine kinase.     

分子靶向药物在肝细胞肝癌治疗中的研究进展

对于不适宜手术切除的晚期肝细胞肝癌,传统的化疗并不能改善患者的预后。分子靶向药物的出现为肝细胞肝癌的治疗提供了新的治疗手段。分子靶向药物治疗肝细胞肝癌的临床试验中,包括多靶点抑制剂、血管内皮生长抑制剂、小分子酪氨酸激酶抑制剂以及分子靶向药与化疗的联合等已经显示出了潜在的疗效和良好的发展前景。临床试验显示索拉非尼可延长肝细胞肝癌的中位无疾病进展时间至9.2个月,中位总生存至10.5个月,贝伐单抗与厄洛替尼联合治疗肝细胞肝癌延长中位总生存达68周。本文针对肝细胞肝癌使用多靶点抑制剂、血管内皮生长抑制剂等的临床研究进展进行综述。     

EGFR inhibitors: what have we learned from the treatment of lung cancer?

Tyrosine kinase inhibitors directed against the epidermal growth factor receptor (EGFR) are the first molecular-targeted agents to be approved in the US and other countries for the treatment of advanced non-small-cell lung cancer after failure of chemotherapy. Some patient characteristics, such as never-smoking, female gender, East Asian origin, adenocarcinoma histology, and bronchioloalveolar subtype, are associated with a greater benefit from treatment with EGFR inhibitors. Recently, studies have identified gene mutations targeting the kinase domain of the EGFR that are related to the response to inhibitors. Most EGFR mutations predict a higher benefit from treatment compared with wild-type receptors and are correlated with clinical features related to better outcome; some EGFR mutations, however, confer drug resistance. The analysis of material usually available from lung cancer patients, using techniques such as direct sequencing to determine EGFR mutational status, can be technically challenging. In this regard, high EGFR copy number and EGFR protein detected by immunohistochemistry can also be used to select those patients who would benefit from treatment. Prospective validation of biological and clinical markers of sensitivity needs to be performed.     

Targeting epidermal growth factor receptor: novel therapeutics in the management of cancer

Overexpression of epidermal growth factor receptor (EGFR) in epithelial tumors, including head and neck, lung, breast, colon and other solid tumors, has frequently been correlated with poor prognosis, thus stimulating efforts to develop new cancer therapies that target EGFR. Monoclonal antibodies and tyrosine kinase inhibitors specifically targeting EGFR are the most well-studied and hold substantial promise of success. Several compounds of monoclonal antibodies and tyrosine kinase inhibitors targeting EGFR have been studied and clinical trials are now underway to test the safety and efficacy of these targeting strategies in several human tumors. This review will address each of these agents alone or in combination with radiation or chemotherapy and highlight some of these promising developments. Cetuximab (Erbitux) is being evaluated in combination with radiation or chemotherapy in Phase III trials. Other compounds such as h-R3, ABX-EGF, EMD-55900 and ICR-62 have proved to be effective in targeting malignant cells alone or in combination with traditional therapies. Tyrosine kinase inhibitors targeting the intracellular domain of EGFR, including ZD-1839 (gefitinib, Iressa), OSI-774 (Erlotinib/Tarceva), PD-153053, PD-168393 and CI-1033, have been studied in clinical setting alone or in combination with radiation or chemotherapy. ZD-1839 is being studied in a Phase III trial in patients with advanced non-small cell lung cancer. EGFR targeted treatment by monoclonal antibodies and tyrosine kinase inhibitors have been proven to sensitize tumor cells to the effects of chemotherapy and radiation therapy. The synergistic activities and nonoverlapping toxicities of these compounds allow concomitant administration with cytotoxic therapy. Challenges of evaluating EGFR targeted agents exist in selecting the optimal dosages and determining long-term toxicity.     

Tyrosine Kinase Inhibitors in EGFR-Mutated Large-Cell Neuroendocrine Carcinoma of the Lung? A Case Report

Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a high-grade carcinoma belonging to the neuroendocrine tumors of the lung and is different from typical lung large-cell carcinoma. It represents about 3% of all pulmonary malignancies and is characterized by neuroendocrine cytologic features. The treatment usually is platinum-based chemotherapy, however the outcome remains poor. Therefore new therapeutic options are needed. Tyrosine kinase inhibitors have demonstrated greater efficacy and better tolerability than standard chemotherapy in non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations. EGFR gene mutations were also rarely identified in LCNEC. We report a patient with lung LCNEC activating EGFR mutations who showed an impressive response to gefitinib.Key words: Large-cell neuroendocrine carcinoma, Epidermal growth factor receptor mutation, Tyrosine kinase inhibitors, Gefitinib     

Targeted therapy in refractory thyroid cancer: current achievements and limitations

Thyroid cancer refractory to conventional treatments lacks effective treatment. Targeted therapy is an emerging therapeutic strategy for these cancers, based on preliminary promising results. Tyrosine kinase inhibitors target both specific oncogenic pathways involved in thyroid cancer progression and aspecific mechanisms such as neoangiogenesis. They are generally well tolerated and most adverse events have low-to-moderate severity. Other classes of drugs have been tested, alone or in combination with tyrosine kinase inhibitors, but so far the results have been limited. The aim of this article is to describe the benefits and limitations of innovative drugs that are currently under investigation in patients with refractory thyroid cancer.