用于乳腺癌的分子靶向治疗药物研究进展

肿瘤的分子靶向治疗是癌症的现代治疗手段。相对于传统的化学治疗而言,分子靶向治疗具有特异性强、用药量低、毒副作用小、人体耐受性好等优点,应用前景广泛。近年此类药物在乳腺癌的临床治疗中取得显著疗效,本文分别对以HER－2为靶点的药物、以表皮生长因子受体（ EGFR）为靶点的药物、以肿瘤血管生成为靶点的药物以及其它新靶点的药物在乳腺癌中的研究现状、临床治疗现状及应用前景进行总结及展望。     

分子靶向药物治疗非小细胞肺癌的临床研究进展

分子靶向药物是利用肿瘤细胞与正常细胞之间分子细胞生物学上的差异,采用封闭受体、抑制血管生成、阻断信号传导通路等方法作用于肿瘤细胞特定的靶点,特异性地抑制肿瘤细胞的生长,促使肿瘤细胞凋亡.分子靶向治疗比传统的化疗特异性强、毒副反应小,将成为今后肿瘤治疗的新趋势.综述了近年来分子靶向药物治疗非小细胞肺癌的临床研究和应用.     

恶性肿瘤的分子靶向检测与靶向治疗

近几年,随着对恶性肿瘤发生和发展分子机理的深入研究,肿瘤靶向治疗在肿瘤的治疗领域发挥着越来越重要的作用.由于靶向治疗药物是针对某种恶性肿瘤细胞所特有的靶点进行抑制、阻断和攻击,因此检测肿瘤中是否存在靶向药物作用的相应分子靶点,已成为临床医师实施靶向药物治疗的依据.     

病理诊断的新领域——肿瘤的分子靶向治疗

分子靶向治疗是当今肿瘤临床研究中最活跃的领域之一,肿瘤靶向治疗已开始在肿瘤治疗中发挥着越来越重要的作用。靶向治疗的效果取决于靶向药物自身的特性和肿瘤是否存在靶向药物作用的相应分子靶点,由此药物病理学应运而生。在靶向治疗的新模式中,病理医师不仅要作出疾病的诊断,提供肿瘤的预后指标,而且还要检测肿瘤中是否存在靶向药物相应的分子靶点,以作为临床医师实施靶向药物治疗的依据。突显出在靶向治疗中病理医师与临床医师合作的重要性,     

乳腺癌靶向治疗药物的研究进展

目的:了解乳腺癌靶向治疗药物的相关研究进展。方法:依据文献,对分别以人类表皮生长因子受体2(HER-2)、磷脂酰肌醇激酶/雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路、细胞周期依赖性激酶、血管新生过程为靶点的4类乳腺癌治疗药物的前沿研究进行综述,并分析其特点。结果与结论:以HER-2为靶点的药物主要有赫赛汀、酪氨酸激酶抑制剂、拉帕替尼以及帕妥珠单克隆抗体;以PI3K/Akt/mTOR信号通路为靶点的药物主要有驮瑞塞尔、依维莫司;以细胞周期依赖性激酶为靶点的药物主要有黄酮吡多;以血管新生过程为靶点的药物主要有贝伐珠单抗。多靶点乳腺癌治疗药物的设计已成为乳腺癌靶向药物研究的前沿和热点。     

肿瘤分子靶向药物耐药性研究进展

目的：综述肿瘤分子靶向药物的作用靶点、耐药机制和逆转措施。方法：应用Pubmed和CNKI期刊全文数据库检索系统,以“肿瘤”、“耐药性”、“靶向药物”和“逆转耐药”为关键词进行检索。纳入标准：①靶向药物的分子靶点;②靶向耐药的机制;③逆转靶向药物的耐药性,共筛选出相关文献32篇。结果：靶向药物的分子靶点以细胞膜受体和细胞内激酶为主,其耐药机制主要包括细胞信号转导、基因突变、肿瘤干细胞、肿瘤微环境、肿瘤细胞代谢和上皮-间质转化等。个体化用药、联合用药、改善肿瘤微环境以及研发新药等措施有望逆转靶向耐药。结论：靶向药物的分子靶点多样,耐药机制复杂,应该积极采取措施加以预防和逆转。     

非小细胞肺癌分子靶向治疗的最新研究进展

随着肿瘤生物学、基因组学和分子生物学的发展,靶向治疗的研究和临床应用已成为当前肺癌领域的热点。本文对国内外有关非小细胞肺癌分子靶向治疗的靶点和主要药物进行了综述。首先概括了表皮生长因子受体抑制剂,其次总结了肿瘤血管生成抑制剂,包括抗血管内皮生长因子单克隆抗体、血管内皮抑素和金属蛋白酶抑制剂的研究,最后对新的靶点EML4-ALK抑制剂的研发进行了跟踪。未来肺癌靶向治疗药物的开发和临床应用会达到更加成熟的阶段。     

分子靶向治疗乳腺癌临床分析

通过文献回顾结合临床观察综述性地介绍了以HER-2为靶点、以表皮生长因子受体（EGFG）为靶向、以肿瘤血管生成为靶点酪氨酸激酶抑制剂、目前正在研究当中的新型分子靶向治疗药物四类药物。分子靶向治疗已经成为手术、放化疗和内分泌治疗后乳腺癌的第四类治疗手段,并且已经在临床当中大面积使用。该治疗模式相信将是未来乳腺癌治疗的潮流。当人们对肿瘤发生发展因素的越发了解,并且依靠先进生物医学手段,将会有更多药物纳入到分子靶向治疗的临床应用当中,届时当有更多的患者受益。     

抗肿瘤单克隆抗体药物研究进展

抗肿瘤细胞表面抗原的单克隆抗体(单抗)可以有效治疗肿瘤.这些单抗药物可通过直接作用于肿瘤细胞、改变机体免疫应答、运送药物和重新激发机体免疫等机制来抗击肿瘤.此文就单抗治疗肿瘤的作用靶点、机制、代表性药物和新策略进行综述.     

作用于Met靶点的非小细胞肺癌治疗药物研究进展

继表皮生长因子受体(EGFR)基因突变和间变性淋巴瘤激酶(ALK)基因融合之后,Met基因激活突变和扩增被认为是非小细胞肺癌(NSCLC)下一个重要的驱动基因,它与肿瘤的增殖、侵袭、转移及血管生成密切相关,已成为靶向治疗领域研究的一大亮点。主要靶向治疗药物可分为抗HGF单克隆抗体、抗c-Met单克隆抗体和小分子抑制剂3类,并多已进入临床试验阶段。对作用于Met靶点的非小细胞肺癌治疗药物的研究进展进行综述。     

抗体偶联药物及其体内外代谢的研究进展

抗体偶联药物（ADC）是由单克隆抗体和细胞毒性有效载荷通过连接子偶联而成,结合了单克隆抗体的高特异性靶向能力和细胞毒活性小分子高效杀伤作用的优点,实现了对癌细胞的精准高效清除,已成为抗癌药物研发的热点之一。自2000年美国食品药品监督管理局（FDA）批准第一个ADC药物吉妥珠单抗（Mylotarg）以来,迄今全球已有14个ADC药物获批上市。这类新型的抗癌药物正引领癌症靶向治疗的新时代。基于ADC药物的构建核心和抗肿瘤作用机制,对ADC药物的体内外代谢的研究进展进行综述,以期从代谢角度为ADC药物的设计、开发、临床前药理、毒理及后续研究提供参考。     

The development of antibody delivery systems to target cancer with highly potent maytansinoids

Improving the tumour selectivity of cytotoxic drugs through conjugation to tumour-reactive monoclonal antibodies may lead to novel, more potent agents for cancer therapy. The maytansinoid drugs are 100- to 1000-fold more cytotoxic in vitro than current clinical anticancer drugs. We recently demonstrated that conjugation of maytansinoid drugs to monoclonal antibodies renders them highly efficacious against cancers of breast and colon in both in vitro and in in vivo tumour models. Antibody-maytansinoids represent a new generation of immunoconjugates that may yet fulfil the promise of effective cancer therapy through antibody targeting of cytotoxic agents.     

Novel approaches for targeted cancer therapy

The clinical use of chemotherapeutic agents against malignant tumors is successful in many cases but suffers from major drawbacks. One drawback is lack of selectivity, which leads to severe side effects and limited efficacy; and another is the emergence/selection of drug-resistance. To limit non-specific toxicity and to improve the efficiency of cancer therapy, "tumor markers", which are proteins generally overexpressed on the surface of tumor cells, can be selectively targeted. Growth factor receptors are one of the most extensively studied tumor markers. The implication of growth factor receptors in the pathogenesis and evolution of cancer has clearly been established and therefore, provides a rationale for therapeutic intervention. The targeting of cytotoxic substances to tumor markers with "magic bullets" is an old idea that raised high expectations but also disappointment. Over the past decade, newly gained understanding of mechanisms for targeted therapy have brought new hopes. Pharmacological agents that selectively target and block the action of growth factors and their receptors have been attempted, such as monoclonal antibodies (mAbs) (whole molecule or fragments), bispecific antibodies, mAbs conjugated to drugs, toxins or radioisotopes, small peptidic and peptidomimetic molecules in free form or conjugated to drugs, anti-sense oligonucleotides, immunoliposomes-encapsulated drugs, and small molecule inhibitors. This review will focus on current developments of selective targeting and bypassing drug resistance in the management of growth factor receptor-overexpressing tumors.     

From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage

Targeted therapies by means of compounds that inhibit a specific target molecule represent a new perspective in the treatment of cancer. In contrast to conventional chemotherapy which acts on all dividing cells generating toxic effects and damage of normal tissues, targeted drugs allow to hit, in a more specific manner, subpopulations of cells directly involved in tumor progression. Molecules controlling cell proliferation and death, such as Tyrosine Kinase Receptors (RTKs) for growth factors, are among the best targets for this type of therapeutic approach. Two classes of compounds targeting RTKs are currently used in clinical practice: monoclonal antibodies and tyrosine kinase inhibitors. The era of targeted therapy began with the approval of Trastuzumab, a monoclonal antibody against HER2, for treatment of metastatic breast cancer, and Imatinib, a small tyrosine kinase inhibitor targeting BCR-Abl, in Chronic Myeloid Leukemia. Despite the initial enthusiasm for the efficacy of these treatments, clinicians had to face soon the problem of relapse, as almost invariably cancer patients developed drug resistance, often due to the activation of alternative RTKs pathways. In this view, the rationale at the basis of targeting drugs is radically shifting. In the past, the main effort was aimed at developing highly specific inhibitors acting on single RTKs. Now, there is a general agreement that molecules interfering simultaneously with multiple RTKs might be more effective than single target agents. With the recent approval by FDA of Sorafenib and Sunitinib--targeting VEGFR, PDGFR, FLT-3 and c-Kit--a different scenario has been emerging, where a new generation of anti-cancer drugs, able to inhibit more than one pathway, would probably play a major role.     

HER2阳性乳腺癌靶向治疗药物的临床研究进展

乳腺癌已成为全球最常见的癌症,人表皮生长因子受体2（HER2）阳性乳腺癌恶性程度较高,早期易复发和转移,总体预后较差。HER2阳性乳腺癌的治疗因靶向药物的不断问世而呈现更多可能,这类药物包括单克隆抗体（曲妥珠单抗、帕妥珠单抗）、酪氨酸激酶抑制剂（奈拉替尼、拉帕替尼、吡咯替尼、图卡替尼）、抗体药物偶联物（T-DM1、DS-8201）。对HER2阳性乳腺癌靶向治疗药物的最新临床试验结果进行综述,以期为该类乳腺癌的临床用药提供参考。     

A combined approach with rituximab plus anti-TRAIL-R agonistic antibodies for the treatment of haematological malignancies

Molecular targeted therapies have changed the landscape of cancer research. Agonistic monoclonal antibodies (MoAbs) targeting TRAIL-death receptors (TRAIL-Rs) have been developed and currently used in clinical trials. Binding of such antibodies to TRAIL-R1 and TRAIL-R2 results in death inducing signalling complex (DISC) formation and induction of apoptosis, which represents a natural mechanism of cell growth control and an ideal target for drug development. These novel fully humanized compounds have been associated with conventional chemotherapy in the treatment of advanced solid malignancies, including different types of lymphoma. Here we outline the rationale and potential of a new molecular-based strategy combining agonistic anti-TRAIL-death receptor monoclonal antibodies plus the pioneer of the new biological frontiers of cancer therapy: rituximab.     

Regulating TRAIL receptor-induced cell death at the membrane : a deadly discussion

The use of TRAIL/APO2L and monoclonal antibodies targeting TRAIL receptors for cancer therapy holds great promise, due to their ability to restore cancer cell sensitivity to apoptosis in association with conventional chemotherapeutic drugs in a large variety of tumors. TRAIL-induced cell death is tightly regulated right from the membrane and at the DISC (Death-Inducing Signaling Complex) level. The following patent and literature review aims to present and highlight recent findings of the deadly discussion that determines tumor cell fate upon TRAIL engagement.     

靶向尿激酶型纤溶酶原激活物受体的抗肿瘤药物的研究进展

尿激酶型纤溶酶原激活物受体（u PAR）是一种糖基磷脂酰肌醇锚定的膜蛋白,已被发现在多种癌细胞中过表达,这一特性使得uPAR成为治疗癌症的一个理想靶标。目前,多种以u PAR为靶点的抗癌药物已被开发,主要包括多肽、单克隆抗体、配体靶向毒素。此外,u PAR作为靶点也已在纳米药物递送系统和光热疗法（PTT）/光动力疗法（PDT）中得到应用。因此就靶向uPAR的抗肿瘤药物的研究进展做一综述。