胃癌分子靶向治疗的现状和展望

目前胃癌的细胞毒药物治疗已进入一个平台期。随着分子生物学研究的深入开展,胃癌的诊断及治疗进入了分子水平。大量的基础和临床研究正在探索胃癌的分子靶点包括:人表皮生长因子受体2、人表皮生长因子受体1、哺乳动物雷帕霉素靶蛋白、血管内皮生长因子、血管内皮生长因子2、纤维母细胞生长因子受体2、肝细胞生长因子受体以及聚腺苷酸二磷酸核糖转移酶等。目前,仅有人表皮生长因子受体2的靶向药物曲妥珠单抗及血管内皮生长因子受体2靶向药物ramucirumab被III期临床研究证实在晚期胃癌中有显著疗效,针对上述靶点的其他药物需进一步研究和开发。     

EGFR-TKI在EGFR突变非小细胞肺癌治疗中的应用现状及进展

表皮生长因子受体（EGFR）突变是非小细胞肺癌（NSCLC）中最常见的致癌驱动因素。表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKI）广泛应用于肺癌治疗中,特别是晚期NSCLC的一线治疗,与标准化疗相比,EGFR-TKI单药治疗已获得较好的疗效及耐受性。而EGFR-TKI在新辅助治疗、辅助治疗及晚期一线与其他药物联合治疗中的疗效尚未明确,获得性耐药成为了限制其疗效的主要问题。分子靶向治疗是驱动基因指导下的治疗,开启了非鳞非小细胞肺癌“个体化”与“精准”治疗时代。本文就EGFR-TKI治疗NSCLC的临床价值及耐药机制进行综述。     

晚期胃癌分子靶向治疗进展

胃癌是消化系统常见的恶性肿瘤之一,大多数患者诊疗时已处于疾病晚期,近10余年来晚期胃癌的治疗没有重大突破,化疗的有效率较低,中位生存期7—9个月,2年生存率〈10％。针对肿瘤细胞生长及血管生成等靶点的分子靶向治疗是目前进展期胃癌治疗领域研究的热点。本文简要概述表皮生长因子受体（EGFR）、血管内皮生长因子（VEGF）、哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的靶向药物如曲妥珠单抗、西妥昔单抗、埃罗替尼、吉非替尼、贝伐单抗、RAD001（everolimus）等在晚期胃癌治疗中的报道。     

放疗联合表皮生长因子受体酪氨酸激酶抑制剂药物治疗晚期非小细胞肺癌的研究进展

靶向药物表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)通过竞争性阻断表皮生长因子受体(EGFR)转导的自身磷酸化、调控细胞周期、阻碍肿瘤细胞DNA损伤修复以及抑制新生血管形成等,起到放疗增敏的效果,同时不增加毒副反应的发生。目前放疗联合EGFR-TKI药物在治疗晚期非小细胞肺癌(NSCLC)及转移灶的临床应用中已显示出一定的疗效优势,有望成为EGFR突变的NSCLC优势人群另一项重要的治疗措施。     

分子靶向药物治疗肺癌的皮肤不良反应预防及护理

分子靶向治疗是针对肿瘤细胞中的一个靶点或几个靶点达到抑制肿瘤细胞增殖的作用。在肺癌二线治疗中,靶向药物已达到与化疗药物相同的疗效。特罗凯和易瑞沙是口服选择性表皮生长因子受体酪氨酸激酶抑制剂,用于晚期非小细胞肺癌（NSCLC）二／三线治疗。     

表皮生长因子受体抑制剂皮肤不良反应的护理

表皮生长因子受体抑制剂(epidermal growth factor receptorinhibitors,EGFRIs)应用于以表皮生长因子受体(EGFR)为靶点进行抗肿瘤的分子靶向疗法,包括单克隆抗体以及小分子酪氨酸激酶抑制剂,在非小细胞肺癌、结直肠癌、胰腺癌等实体瘤治疗中发挥重要作用.     

乳腺癌HER-2靶向治疗的现状与发展前景

目的人表皮生长因子受体2(HER2)是表皮生长因子受体(EGFR或Er Bb)家族中扮演中心角色的一个成员。本文对HER2靶向治疗的现状与发展方向作一综述。方法查阅Pubmed、中国知网、万方、维普等数据库与乳腺癌HER2靶向治疗方面相关的文章,共纳入52篇文献。结果 HER2信号能够调节细胞增殖、存活和分化,与乳腺癌、胃癌、肺癌与卵巢癌等多种肿瘤的发生发展密切相关。目前使用的HER2靶向治疗有助于改善临床化疗药物疗效、提高患者无疾病生存期和5年存活率,但肿瘤的耐药性也越来越严重,已经引起人们的关注。结论 HER2靶向治疗对提高HER2阳性乳腺癌患者治疗效果起到重要作用,其耐药性需要进一步研究解决。     

拉帕替尼联合化疗药物治疗晚期乳腺癌患者的不良反应观察及护理

拉帕替尼是一种可逆性酪氨酸激酶抑制剂,适用于治疗人类表皮生长因子受体2（HER2）过度表达且经蒽环类、紫杉类药物和曲妥珠单抗治疗后复发的晚期或者转移性乳腺癌。作用机制是通过抑制细胞内的表皮生长因子受体1（ErbB-1）和表皮生长因子受体2（ErbB-2）的ATP位点阻止肿瘤细胞磷酸化和激活,通过ErhB-1和ErbB-2的同源和异源二聚体阻断下调信号,     

表皮生长因子受体-酪氨酸激酶抑制剂在治疗非小细胞肺癌方面的研究进展

肺癌中80%~85%为非小细胞肺癌(non-small cell lungcancer,NSCLC)。随着药学及分子生物学的快速发展,分子靶向治疗已成为非小细胞肺癌药物研究的热点。分子靶向药物主要包括表皮生长因子受体(epidermal growth factor receptor,EGFR)家族抑制剂、血管生成抑制剂、多靶点的酪激酶抑制剂及其他几类药物等。表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)在晚期NSCLC治疗方面取得了巨大进展,目前国内外上市的已有三代。本文分别对三代EGFR-TKIs代表药物(吉非替尼、阿法替尼、奥希替尼)的作用机制、临床研究、不良反应和耐药情况进行了综述。     

靶向治疗药物拉帕替尼治疗转移性或晚期乳腺癌的护理

拉帕替尼是小分子4-苯胺基喹唑啉类受体酪氨酸激酶抑制剂,抑制表皮生长因子受体和人表皮因子受体,从而抑制肿瘤生长。我院是以治疗肿瘤为中心的专科医院,抗肿瘤药物化疗、靶向治疗是肿瘤科室主要治疗手段之一[1-3]。2008年2月—2012年4月我科应用拉帕替尼治疗转移性或晚期乳腺癌病人10例,取得良好的疗效,现将观察结果及护理经验总结如下。     

Immunotherapy in hepatocellular carcinoma: Combination strategies

Liver cancer is one of the most common causes of cancer death globally, and its incidence in the United States is increasing. Patients with advanced hepatocellular carcinoma (HCC) who are not candidates for surgical resection, liver transplant, or locoregional therapies can be treated with systemic therapies. Multiple agents, including sorafenib, lenvatinib, and regorafenib are approved for use as either first- or second-line therapy in this patient population, but all have relatively modest survival benefits. HCC is potentially susceptible to therapy with checkpoint inhibitors, including agents such as nivolumab and pembrolizumab, which are both approved by the Food and Drug Administration for patients previously treated with sorafenib but have not demonstrated superior overall survival in phase III trials. It is clear that more effective approaches are needed to potentiate the effects of checkpoint inhibitors in patients with HCC. This review will outline and appraise the current literature on the use of checkpoint inhibitors in HCC as part of a combination treatment involving an additional mode of therapy. The list of agents that can be paired with checkpoint inhibitors includes an additional checkpoint inhibitor, vascular endothelial growth factor or vascular endothelial growth factor receptor inhibitors, tyrosine kinase inhibitors, OX-40 agonists, and PT-112 inhibitors. The main non-pharmacologic therapies currently being studied for inclusion in a combination strategy include radiation therapy, trans-arterial chemoembolization, and ablation.     

Pembrolizumab for the first-line treatment of non-small cell lung cancer

Introduction: Platinum-based chemotherapy had long played a role as standard therapy for the first-line treatment of advanced or recurrent non-small cell lung cancer (NSCLC). However, immune checkpoint inhibitors such as pembrolizumab, a monoclonal antibody that prevents programmed death protein 1 (PD-1) receptor, have brought a paradigm shift in this field.

Areas covered: In this article, we review the relevant literatures and ongoing trials on the first-line treatment of pembrolizumab. Especially, in two pivotal phase III trials, KEYNOTE-024 and ?189, both pembrolizumab monotherapy and combined pembrolizumab plus chemotherapy significantly prolonged overall survival (OS) compared to the existing platinum-based chemotherapy. Currently, multiple trials with combination therapy of pembrolizumab and other agents have been conducted, and further evidences are expected to be created.

Expert opinion: Immune checkpoint inhibitors that block the PD-1/PD-L1 pathway are essential drugs for advanced or recurrent NSCLC, among which pembrolizumab becomes one of the standards of care in the first-line of NSCLC. For further improvement in efficacy of pembrolizumab, it is necessary to clarify the identification of biomarkers exclusive to PD-L1 expression, predictive factors for patients who benefit most from the agent.     

Overview of systemic treatment in recurrent and advanced cervical cancer: a primer for radiologists

Imaging has a central role in surveillance of cervical cancer, guiding decision on when to initiate treatment for recurrent disease and to guide management in advanced cervical cancer. Due to the increased availability of pelvic radiation therapy, the rate of atypical presentation of recurrent disease has increased. Simultaneously, the array of systemic therapies now available for advanced cervical cancer has considerably expanded in the last few years, with therapies now available in mid and low-income countries. While pelvic recurrences are amenable of loco-regional treatment, recurrent disease may present with metastases to the thoracoabdominal organs, lymph nodes, bones, skin and brain, for which systemic treatment represent the standard of care. Besides combined chemotherapy regimens, alternative chemotherapies, biosimilars and immune checkpoint inhibitors are now available, each associated with a definite pattern of response and toxicity. In this review, after describing the typical and atypical presentations of recurrent and advanced cervical carcinoma on cross-sectional imaging, we will discuss systemic treatment for recurrent or advanced disease and their associated radiographic sequelae, in light of the newly available therapies.

     

Gefitinib (Iressa, ZD1839) and tyrosine kinase inhibitors: the wave of the future in cancer therapy

Targeted therapies are one of the latest innovative trends in cancer therapy. The epidermal growth factor receptor (EGFR) is a target found in high concentrations in several solid tumors including lung, breast, colorectal, and brain. Tyrosine kinase inhibitors, such as gefitinib (Iressa, ZD1839), block the EGFR. As a result, there is inhibition of cellular proliferation, promotion of apoptosis, and inhibition of anti-angiogenesis. Gefitinib has demonstrated significant efficacy in non-small-cell lung cancer (NSCLC), leading to FDA approval for treatment of this refractory disease. Phase 2 trials with gefitinib for platinum refractory NSCLC reported disease response and symptom improvement. Early results of phase 2 studies of gefitinib, combined with standard chemotherapy in colorectal cancer, showed a 75% response rate compared with 55% with standard therapy alone. Gefitinib, combined with flutamide, produced an additive growth inhibition in prostate cancer. A phase 2 trial of gefitinib in first-relapse glioblastoma multiforme demonstrated median overall survival from treatment start of 39.4 weeks compared with 40 weeks with standard chemotherapy. Gefitinib is an oral agent with a mild toxicity profile, and thus, may be an optimal addition to chemotherapeutic regimens for some solid tumors. Gefitinib is potentially a vital and useful weapon in the arsenal of cancer therapies.     

Colorectal cancer

Cancers of the colon and rectum will affect 1 in 17 North Americans during their lifetime. The progress witnessed in the treatment of these cancers in recent years has been remarkable. Improvements have been realized in surgical technique, radiation therapy, and systemic therapies, particularly with the addition of oxaliplatin and irinotecan to the previously limited armamentarium of fluorouracil alone. Targeted therapies directed at the vascular endothelial growth factor pathway and the epidermal growth factor pathway are now key players in the treatment of colorectal cancer. With current-day therapies, more than 75% of patients with localized disease are recurrence free at 3 years, and up to 50% of patients with advanced unresectable disease are alive at 2 years. This review focuses on the evidence supporting the current role of chemotherapy and radiation therapy in the adjuvant management of colorectal cancers and the strategy of combining chemotherapy and biological therapy in the treatment of metastatic disease.     

The role of epidermal growth factor receptor in advanced non-small cell lung carcinoma

Chemotherapy is the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Over the past 20 years, advances in chemotherapy have shown minimal incremental improvement in the survival outcomes of patients with advanced NSCLC. With the identification of molecular and genetic alterations in lung cancer, several new potential rationally designed therapeutic targets have emerged. One of these is the epidermal growth factor receptor (EGFR) and member of the ErbB family of receptor tyrosine kinases. Several inhibitors, both antibodies directed at the extra-cellular portion of the receptor, and small molecule inhibitors directed at the tyrosine kinase domain of EGFR are in clinical development in lung cancer. This article will review the pre-clinical rationale and the clinical studies of EGFR inhibitors alone and/or in combination with chemotherapy that have been performed to date in advanced NSCLC.     

New directions in oncology nursing care: focus on gefitinib in patients with lung cancer

Treatment of solid tumors with chemotherapy regimens commonly is associated with debilitating or life-threatening side effects. Careful patient management, appropriate and prompt management of side effects, and interruption of therapy frequently are required for patients receiving chemotherapy. Furthermore, the systemic toxicity associated with chemotherapy may result in irreversible and incapacitating side effects, such as peripheral neuropathy, that lead to poor quality of life in patients. Gefitinib (Iressa, ZD1839, AstraZeneca Pharmaceuticals LP, Wilmington, DE) is a biologically based, molecular targeted therapy with a novel mechanism of action: selective inhibition of the epidermal growth factor receptortyrosine kinase (EGFR-TK) activity. Once-daily oral treatment with gefitinib is well tolerated. In clinical trials, treatment with gefitinib resulted in durable tumor responses and improvement in lung cancer-related symptoms in patients with advanced non-small cell lung cancer who had received prior chemotherapy. Trials are under way to explore the full potential of gefitinib and additional EGFR-TK inhibitors for other solid tumors and in other treatment settings, including prevention. Biologically based, molecular-targeted therapies such as gefitinib are providing new treatment options for patients and adding a new dimension to clinical practice for oncology nurses.     

The role of epidermal growth factor receptor in advanced non‐small cell lung carcinoma

Chemotherapy is the standard of care for patients with advanced non‐small cell lung cancer (NSCLC). Over the past 20 years, advances in chemotherapy have shown minimal incremental improvement in the survival outcomes of patients with advanced NSCLC. With the identification of molecular and genetic alterations in lung cancer, several new potential rationally designed therapeutic targets have emerged. One of these is the epidermal growth factor receptor (EGFR) and member of the ErbB family of receptor tyrosine kinases. Several inhibitors, both antibodies directed at the extra‐cellular portion of the receptor, and small molecule inhibitors directed at the tyrosine kinase domain of EGFR are in clinical development in lung cancer. This article will review the pre‐clinical rationale and the clinical studies of EGFR inhibitors alone and/or in combination with chemotherapy that have been performed to date in advanced NSCLC.     

Epidermal growth factor receptor tyrosine kinase inhibitors: evolving role in the treatment of solid tumors

Inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) activity have shown promise as novel anticancer agents in a variety of common solid tumors. In preclinical studies and phase I trials, tumor responses to EGFR-TK inhibitors (EGFR-TKIs), such as gefitinib (Iressa, AstraZeneca Pharmaceuticals LP, Wilmington, DE) and erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY, and Genentech, Inc., South San Francisco, CA) were observed in heavily pretreated patients with advanced non-small cell lung cancer (NSCLC), head and neck cancer, breast cancer, colorectal cancer, and other solid tumors. Subsequent phase II studies resulted in tumor responses, disease stabilization, symptom improvement, and improved quality of life in patients with advanced NSCLC who had received prior platinum-based chemotherapy or platinum and docetaxel chemotherapies. Side effects related to treatment with EGFR-TKIs were generally mild, reversible, and noncumulative. Severity and frequency of drug-related adverse events were related directly to dose. The potential role of EGFR-TKIs in treating other solid tumors currently is being studied. Furthermore, research is being conducted to explore the potential use of EGFR-TKIs in novel combinations with chemotherapy, radiation therapy, endocrine therapy, and other molecular targeted therapies.