分子诊断技术和靶向治疗在乳腺癌个体化治疗中的应用

乳腺癌是一类由不同病理实体构成和具有多样临床行为表现的异质性疾病。乳腺癌分子诊断技术和靶向治疗由于特异性较强、疗效明确、不良反应相对较小,已成为继手术、放疗和化疗等传统治疗模式之后的一种全新治疗手段。本文阐述分子靶向治疗在乳腺癌个体化治疗中的现状和应用。     

Novel targeted therapies for the treatment of penile cancer

Introduction: The treatment of penile cancer has changed over the past decade in that it was primarily a surgically managed disease and those with locally advanced or metastatic disease uniformly had a very poor prognosis. However, with the use of better traditional systemic chemotherapeutic agents in the neoadjuvant and adjuvant settings, the disease-specific survival and general outlook has improved. However, there is still a large group of patients who will progress even while on systemic therapy. It is in those patients where the application of targeted therapies has been investigated with some experiencing partial or even complete responses. With the improvement seen in patients with chemotherapy refractory disease, the application of novel targeted agents in the neoadjuvant setting may have a resultant positive impact on patient survival.

Areas covered: This review includes research pertaining to targeted therapies, biomarkers and signaling pathways involved with penile cancer. The article was based on a literature search using the keywords ‘penile cancer’ and ‘targeted therapies’.

Expert opinion: Penile cancer at the advanced stages of the disease has a high mortality. The utilization of novel targeted therapies in these situations is warranted in combination with, or sequentially with, traditional cytotoxic chemotherapy to improve the patient survival rate. Personalized therapy is nearly here for penile cancer and should be made real within the next decade.     

肿瘤分子靶向治疗药物的应用进展

分子靶向治疗作为肿瘤治疗的新手段,正以其低毒、副反应和高治疗效果成为肿瘤治疗研究的热点.按作用靶点以及药物的性质,分子靶向药物可分为数类,主要包括以EGFR为靶点的药物、作用于HER2/erbB2的单克隆抗体、靶向VEGF/VEGFR的药物、以白细胞CD为靶点的单克隆抗体以及作用于多个靶点的药物.本文综述肿瘤分子靶向治...     

乳腺癌靶向治疗的新策略

目前,乳腺癌的常规治疗手段如化疗、放疗等存在严重的全身副作用,为此,开展乳腺癌的靶向治疗研究具有重大意义。本文综述了乳腺癌靶向治疗的3个研究领域:抗体介导的靶向、微载体介导的靶向、乳腺癌干细胞靶向,并阐述这些治疗策略的基本研究思路,分析这些新的治疗策略面临的一些问题,从而提出解决这些问题的相关见解。     

三阴性乳腺癌靶向治疗研究进展

三阴性乳腺癌（TNBC）作为乳腺癌一种预后较差的亚型,在出现化疗药物抵抗的情况下,由于缺少其他有效治疗方法,疾病往往易快速复发转移。因此针对TNBC新治疗靶点及靶向药物的研究已成为目前国内外研究热点。本文主要针对目前TNBC靶向治疗研究进展进行总结分析,主要包括ADP合同聚合酶抑制剂、抗血管生成靶向药物、抗表皮生长因子受体信号通路靶向药物、雄激素受体拮抗剂、免疫检查点抑制剂、PI3K-AKT-mTOR通路抑制剂等,以期从中找出最有可能成为未来发展方向的靶向治疗方法。     

An update on first line therapies for metastatic breast cancer

Introduction: In recent years, outcomes of patients with metastatic breast cancer (MBC) have improved due to a greater understanding of the mechanisms of carcinogenesis in the development of newer molecularly targeted drugs, especially those as a front-line therapy. Remarkable improvements have been made in the treatment of hormone receptor positive (HR+) and Her2 positive MBC and currently targeted treatment strategies represent a valid first line treatment.

Areas covered: Herein, the authors provide an overview of the first-line pharmacotherapies currently available for the treatment of MBC and provide their expert perspectives on the area.

Expert opinion: Decisions on the first-line treatment of MBC should consider the clinical features of the disease, but also the biological mechanisms that regulate tumor cell growth. New and effective therapeutic agents have recently been introduced in the first-line therapy of MBC. However, to optimize the treatment of patients with metastatic disease, clinicians need biomarkers of resistance or sensitivity to targeted therapies. Efforts must also be made in developing strategies to personalize treatments of MBC patients and to identify those patients who might gain the most benefit from new treatment interventions, to save costs and limit toxicity.     

分子靶向治疗三阴性乳腺癌无进展 生存期的网状Meta分析

目的：网状Meta分析靶向药物治疗三阴性乳腺癌(TNBC)的无进展生存期（PFS）。方法：系统检索PubMed、EMBASE.com、the Cochrane Central Register of Controlled Trials(CENTRAL)、Web of Science(via ISI Web of Knowledge)、BIOSIS Previews(via ISI Web of Knowledge)和Chemical Abstracts(CA)等数据库,追踪三阴性乳腺癌靶向治疗的系统评价或综述的参考文献,纳入靶向药物治疗三阴性乳腺癌的随机对照试验,由2名研究人员独立提取纳入研究的数据,并评价纳入研究的方法学质量,贝叶斯网状Meta分析采用WinBUGS 1.4软件。结果：共纳入13个随机对照试验,包含2307例患者。纳入的研究方法学质量较高。直接比较的Meta分析结果显示：对比单纯化疗,贝伐单抗联合化疗能改善PFS（HR=0.63,95%CI：0.39～0.90）;其他靶向治疗药物联合化疗在改善PFS差异无统计学意义。间接比较的Meta分析结果显示8种干预方案之间在改善患者PFS上差异均无统计学意义。结论：靶向药物联合化疗治疗三阴性乳腺癌具有一定的疗效,然而证据的样本量不足,尚需要更多设计严谨、大样本的随机对照试验深入研究。     

非小细胞肺癌化疗及分子靶向治疗药物的研究进展

非小细胞肺癌(NSCLC)在全世界范围的发病率逐年上升,对人类健康造成严重威胁。经过多年努力,NSCLC的治疗效果明显提高。本文就近年来NSCLC化疗及分子靶向治疗等方面的研究进展加以综述。     

Therapeutic options for metastatic breast cancer

Metastatic breast cancer (MBC) remains an incurable disease despite ongoing therapeutic advances. Recently there has been progress extending the range of available cytotoxic chemotherapy drugs and optimizing their scheduling. In addition, a greater understanding of tumor biology has led to the development of a number of targeted therapies. Several of these newer agents, such as trastuzumab, lapatinib and bevacizumab, have demonstrated activity in combination with chemotherapy and have improved the prognosis of patients with MBC. We hope that further progress elucidating the pathophysiology and biology of MBC will continue to lead to corresponding advances in treatment.     

非小细胞肺癌分子靶向治疗的研究进展

肺癌作为对人类健康与生命造成威胁的一种常见恶性肿瘤,具有较高的发病率与死亡率.肺癌临床属性分为非小细胞肺癌与小细胞肺癌,其中非小细胞肺癌在全部肺癌发病中的占比高达80％～85％,且多数肺癌患者在确诊阶段已处于中晚期,加剧了临床治疗的难度.在医疗技术的不断发展下,手术、放疗、化疗、靶向治疗以及免疫治疗等方式的出现与发展为...     

胰腺癌分子靶向治疗现状及进展

胰腺癌是恶性程度较高的消化系统肿瘤之一,常规治疗效果有限,5年生存率只有5％左右。随着分子生物学研究的进展,EGFR抑制剂、VEGF抑制剂以及基质金属蛋白酶抑制剂等分子靶向药物的研究成为热点之一,本文着重介绍分子靶向治疗的研究现状及进展。     

Ligand-based targeted therapy for cancer tissue

Background: Limited accessibility of drugs to the tumor tissues, the requirement of high doses, intolerable cytotoxicity, the development of multiple drug resistance and non-specific targeting are obstacles to the clinical use of cancer drugs and cancer therapy. Objective: Drug delivery through carrier systems to cancerous tissue is no longer simply wrapping up cancer drugs in a new formulation for different routes of delivery, rather the focus is on targeted cancer therapy. Methods: This review summarizes the exploitation of drug-loaded nanocarrier conjugates with various targeting moieties for the delivery and targeting of anticancer drugs and describes the current status of and challenges in the field of nanocarrier-aided drug delivery and drug targeting. Conclusion: The discovery of targeting ligand to cancer cells and the development of ligand-targeted therapy will help us to improve therapeutic efficacy and reduce side effects. Unlike other forms of therapy, it will allow us to maintain quality of life for patients, while efficiently attacking the cancer tissue. It indicates that ligands have a pivotal role in cancer cell targeting.     

Recent advances in the medical management of breast cancer: highlights from the 29th San Antonio Breast Cancer Conference

The 29th edition of the San Antonio Breast Cancer Symposium was attended by a total of > 8000 basic scientists, translational researchers, clinical investigators and physicians gathering from ~ 80 countries worldwide. This is the largest meeting focusing on breast cancer, encompassing a wide array of topics from prevention, aetiology and diagnosis to molecular biology and treatment. From the main presentations at the meeting, it seems clear that combined efforts at prevention and treatment of this disease have translated into small, but significant, achievements. Much of the research in the area is focused on improving the therapeutic ratio of available treatments by better selection of patients.     

易瑞沙在一线化疗失败非小细胞肺癌的疗效观察

目的观察易瑞沙对一线化疗失败非小细胞癌(NSCLC)的近期疗效、生存期及不良反应。方法将73例一线化疗失败的NSCLC患者随机分为两组,A组36例给予单药多西紫杉醇75 mg·m-2,d1,1次/3周,B组37例给予易瑞沙0.25口服,每日一次,随访观察两组近期疗效、6个月、1年生存率及毒副反应发生情况。结果 B组总缓解率高于A组(P0.05);两组6个月生存率比较差异无统计学意义(P0.05);B组1年生存率高于A组(P0.05);B组除了皮疹、腹泻外其他不良反应发生率低于A组(P0.05)。结论易瑞沙靶向治疗一线化疗失败的NSCLC,可获得较好的近期疗效,延长患者生存期,毒副反应轻,能够改善患者生活质量。     

Efficacy of buparlisib in treating breast cancer

Introduction: Breast cancer is the most frequent cancer in women. Despite a decline in breast cancer mortality, prognosis of advanced breast cancer remains poor. In a desperate need to improve breast cancer outcomes, newer agents that target molecular pathways are being tested. Deregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) is frequently found in breast cancer. This can lead to resistance of endocrine therapy and anti-HER2 therapies. Targeting this pathway may restore sensitivity to these compounds. Buparlisib (BKM-120) is an orally active pan-PI3K inhibitor evaluated in different tumor types.

Areas covered: Buparlisib is one of the most investigated PI3K inhibitors. Preclinical and clinical studies of buparlisib in breast cancer are analyzed and discussed. This article reviews the status of buparlisib, completed and ongoing trials, and its safety.

Expert opinion: PI3K inhibitors show promising results in breast cancer. However, we raise a number of issues including the identification of biomarkers to predict treatment response and strategies to counteract resistance. Moreover, its toxicity profile could limit its extensive use.     

新型辅助化疗在乳腺癌治疗中的临床应用

目的探讨新型辅助化疗法对乳腺癌特别是晚期乳腺癌的作用和疗效。方法选取我院2006年8月-2010年9月收治的160例乳腺癌疾病患者,并按照随机分配的原则分为实验组（80例）,对照组（80例）,实验组采用新型辅助化疗治疗方案（TAC）,对照组采用传统的化疗方法（CAF）,观察指标为腋窝淋巴结和肿瘤的大小、分化变化情况。结果实验组有效例数为63例（78．75％）,明显好于对照组有效例数42例（52．5％）,两组的治疗效果差异有极显著性（P〈0．01）。并且实验组抗癌药物细胞毒性（依照0-IV度毒性分级）也明显低于对照组（P〈0．01）,差异有极显著性。结论新型辅助化疗可以使腋窝淋巴结缩小、降低肿瘤分期、减小病灶、提高保乳手术和治性手术的成功率,值得临床推广。     

Emerging molecular targeted therapies in the treatment of head and neck cancer

Current development of molecular targeted therapies in oncology is particularly active. The aim of this study is to review recent advances in the field of molecular targeted therapies for head and neck squamous cell carcinoma (HNSCC). As EGFR signaling pathway and angiogenesis play a key role in the growth of HNSCC, EGFR with its downstream effectors and molecular factors implicated in the angiogenesis process, such as VEGF and its receptors, represent the main targets of the new therapeutic agents now in development. Today, cetuximab, an anti-EGFR monoclonal antibody, is the only targeted therapy approved for the treatment of HNSCC in patients with locally advanced tumors, in association with radiotherapy, and in patients with recurrent or metastatic diseases. Future progress is expected with the integration of cetuximab into induction chemotherapeutic regimens or in association with concurrent chemoradiotherapy for locally advanced tumors and with the development and evaluation of other molecular targeted therapies such as antiangiogenic drugs. As these innovative molecules start to be used in clinical practice, the identification of predictive markers for efficacy and toxicity becomes a crucial issue.     

纳米药物在肝癌靶向治疗中的研究进展

目的了解肝癌靶向治疗的纳米药物种类及不同靶向机制,为纳米药物的进一步研发提供参考。方法对国内外相关文献进行归纳和综述。结果和结论纳米药物在肝癌靶向治疗中有着独特的优势,具有广阔的研究和开发前景。