靶向药物乳腺癌治疗史上的革命

科学家将那些与肿瘤密切相关的分子称为“分子靶点”，靶向药物专门瞄准这些“靶点”，在高效杀灭癌细胞的同时，健康的正常细胞却毫笺无损。2006年欧洲肿瘤内科学会年会公布的最新研究显示，对HER2阳性晚期乳腺癌，在赫赛汀与多烯紫杉醇联合疗法中添加希罗达，大大延缓了疾病恶化的时间，延长时间达32％。靶向药物希罗达和赫赛汀的临床研究结果被视为乳腺癌治疗史上的革命。[编者按]     

HGF／c-Met信号通路与胃癌相关研究进展

胃癌是世界上最常见的恶性肿瘤之一,主要治疗方式为手术、化疗和放疗,但是,临床效果却不尽如人意。目前针对胃癌靶向治疗仍不理想,单一的靶向治疗易导致耐药及肿瘤复发,多靶点联合用药将是胃癌分子靶向治疗的一个发展趋势。本文介绍了肝细胞生长因子（HGF）／肝细胞生长因子受体（c—Met）信号转导通路参与胃癌的发生、发展和侵袭转移,是极具潜力的胃癌治疗靶点。目前研究中涌现出大量靶向该通路的药物并在临床研究中取得成果,但由于种族及胃癌亚型不同,仍然面临许多挑战。更深入的研究HGF／c-Met信号转导通路的作用机制,多渠道筛选独特分子亚型的胃癌患者用以进行针对性的靶向临床试验等可为胃癌治疗提供新的思路。     

靶向治疗尚不能代替传统治疗

传统化疗药物是癌症治疗药物的主力军，但由于其“地毯式”轰炸的明显副作用，不少患者由于不能耐受而降低治疗标准。分子靶向治疗是在对肿瘤分子生物学了解的基础上，以病变细胞为靶点的治疗，能高效并选择性地杀伤肿瘤细胞，减少对正常组织的损伤，特别是克服了传统化疗药特异性差、毒副作用大的缺点。目前，新兴的分子靶向治疗已在乳腺癌、肺癌等领域取得很好的疗效。     

Herceptin治疗HER-2过表达性乳腺癌研究进展

HER-2是一种与乳腺癌发生、发展密切相关的癌基因,Herceptin是针对HER-2的分子靶向药物,其肿瘤治疗作用受到广泛关注.该文综述近两年来国外在Herceptin治疗HER-2过表达乳腺癌方面的最新研究进展,包括Herceptin作用机制的研究、Herceptin抵抗研究、Herceptin与其它化疗药物特别是与其它分子靶向药物联合用药效果的研究、放射免疫疗法研究以及Herceptin心脏毒性研究.     

乳腺癌靶向药物治疗进展

近年来,乳腺癌的发病率逐年升高,已成为威胁女性健康最常见的恶性肿瘤之一。在乳腺癌的综合治疗中,靶向治疗在乳腺癌的术后辅助治疗与晚期解救治疗中均有不可或缺的地位。近年来,随着对肿瘤发生、发展过程中分子机制的深入研究,乳腺癌的分子靶向药物被广泛应用于乳腺癌治疗,并取得了显著疗效。曲妥珠单抗是最早应用于乳腺癌靶向治疗的药物,其通过特异性地结合Her-2分子胞外段的结构域Ⅳ,可在人体内介导抗体依赖的细胞介导的细胞毒作用     

乳腺癌HER2阳性的分子靶向治疗研究进展

乳腺癌是一个严重危害妇女健康的恶性肿瘤,全世界每年约有135万妇女患乳腺癌,约有33万妇女死于乳腺癌[1].手术、化疗、放疗及内分泌治疗可以使许多患者得到较好的疗效,但仍有25％～30％的乳腺癌患者发生远处转移[2].目前研究发现HER2基因在20％～ 30％的乳腺癌患者中扩增,其过表达与乳腺癌的发生、发展密切相关,并且这部分患者病情重、预后差[3].近年来,随着肿瘤分子生物学研究的日趋深入,乳腺癌的分子靶向治疗越来越被广泛应用,尤其是针对乳腺癌HER2阳性的分子靶向治疗更是越来越受到重视.     

乳腺癌靶向药物治疗进展

<正>近年来,乳腺癌的发病率逐年升高,已成为威胁女性健康最常见的恶性肿瘤之一。在乳腺癌的综合治疗中,靶向治疗在乳腺癌的术后辅助治疗与晚期解救治疗中均有不可或缺的地位。近年来,随着对肿瘤发生、发展过程中分子机制的深入研究,乳腺癌的分子靶向药物被广泛应用于乳腺癌治疗,并取得了显著疗效。曲妥珠单抗是最早应用于乳腺癌靶向治疗的药物,其通过特异性地结合Her-2分子胞外段的结构域Ⅳ,可在人体内介导抗体依赖的细胞介导的细胞毒作用     

肺癌相关分子靶点检测方法及临床应用研究进展

分子靶点检测是分子靶向治疗的前提,临床需要根据患者的分子病理检测结果制定个体化治疗方案和合理选择药物。目前临床对肺癌患者的一些靶点基因检测最为常见,其检测方法也各不同。     

用“生物导弹”治疗肺癌

<正>靶向治疗是目前肺癌的主要治疗手段之一，被人们称为“生物导弹”。那么什么是靶向治疗呢？就是用靶向药物瞄准癌细胞上的分子靶点，对其进行精准“打击”。而体内必须要有相应的靶点，如果没有靶点，就脱靶了，也就没有了治疗效果。     

mTOR信号途径与乳腺癌分子靶向治疗

乳腺癌是女性最常见的恶性肿瘤之一，发病机制复杂，其中涉及到很多信号通路如丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）、磷酸肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）／蛋白激酶B（PKB，protein kinase B，Akt）信号通路的调控。哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）是PI3K／Akt下游的一种重要的丝氨酸-苏氨酸蛋白激酶，与很多癌症的发病与治疗有着密切的关系，它在细胞存活、生长及增殖中都具有重要的作用，mTOR的调节失常往往与乳腺癌的发生相关。分子靶向药物可通过阻断肿瘤细胞或相关细胞的信号转导，来控制细胞基因表达的改变，而产生抑制或杀死肿瘤细胞。作为mTOR的抑制剂，雷帕霉素（Rapamycin）在乳腺癌的分子靶向治疗中得到了越来越多的关注。本文对近几年来有关乳腺癌中mTOR信号通路及其蛋白的表达的研究和Rapamyein在乳腺癌分子靶向治疗中的临床应用等方面作一综述，并对乳腺癌中mTOR信号通路机理研究的意义进行展望。     

乳腺癌内分泌耐药机制的研究进展

乳腺癌是全球发生率最高的肿瘤。在分子分型中,雌激素受体阳性占70%左右,内分泌治疗成为乳腺癌治疗的重要举措之一。但是,一线内分泌治疗平均1年以后出现耐药和疾病进展,转移性乳腺癌难以控制,平均生存期为3年,5年生存率为25%,所以对于耐药机制的把握有利于相关药物的研发,延长患者的生存率,本文就乳腺癌内分泌耐药的主要机制及研究进展进行综述。     

Mechanistic Examination of Walnuts in Prevention of Breast Cancer

Walnuts contain bioactive molecules that may contribute to their beneficial effects, including alpha-linolenic acid (ALA) and phytosterols. In these studies, extracts of walnut, purified compounds, or postprandial serum were examined for effects on breast cancer cell proliferation and gene expression. Extracts derived from walnut oil decreased proliferation of MCF-7 cells, as did ALA and β-sitosterol. The gene expression response of ALA in the mouse breast cancer cell line TM2H indicates this molecule has multiple cellular targets with peroxisome proliferator-activated receptor (PPAR) target genes, liver X receptor (LXR), and farnesoid X receptor (FXR) target genes being affected. In transactivation assays, walnut oil extracts increased activity of FXR to a greater extent than the other tested nuclear receptors. When examined separately, walnut components ALA and β-sitosterol were the most efficacious activators of FXR. When serum from individuals fed walnut components were applied to MCF-7 cells, there was a correlation between body mass index and breast cancer cell proliferation in vitro. Taken together, these data support an effect of walnut and its bioactive constituents on mammary epithelial cells and that multiple molecular targets may be involved.     

Lithocarpus Polystachyus Rehd Leaf Aqueous Extract Inhibits Human Breast Cancer Growth In Vitro and In Vivo

Lithocarpus polystachyus leaves have been used as tea beverage and folk medicine for healthy care in the Southwest of China. The purpose of this study is to investigate the anticancer activity of Lithocarpus polystachyus Rehd leaf aqueous extract (LPAE) and to explore the possible mechanism of its activity. Growth inhibition effects of LPAE breast cancer were tested in vitro and in vivo. The possible mechanism of its activity was analyzed with cell biological and molecular biological assays. After LPAE treatment, the proliferation and colony formation of cancer cells decreased; apoptotic cells increased; DNA fragmentations were evident; mRNA and protein expressions of PPARγ, Bax, and caspase-3 genes increased and expressions of cyclin D1 and Bcl-2 genes decreased; in vivo experiment, LPAE inhibited human beast cancer growth. The findings in this experimental study suggested that LPAE has potential cytotoxic and apoptotic effects on human breast cancer cells in vitro and inhibits the cancer growth in vivo, and its mechanism of activity might be associated with apoptosis induction of cancer cells through upregulation of the mRNA and protein expressions of PPARγ, Bax, and capase-3 genes and downregulation of the expressions of cyclin D1 and Bcl-2 genes.     

Targeting apoptosis is the major battle field for killing cancers

Targeting apoptosis is one of the major strategies for cancer therapy. Essentially, most of the conventional cancer therapeutic drugs that are in the clinical use induce apoptosis and in part necrosis of malignant cells and therefore prevent cancer progression and metastasis. Although these cytotoxic anticancer drugs are important weapons for killing cancers, their toxic side effects limited their application. The molecularly targeted therapeutics that are based on the deeper understanding of the defects in the apoptotic signaling in cancers are emerging and have shown promising anticancer activity in selectively killing cancers but not normal cells. The examples of molecular targets that are under exploration for cancer therapy include the cell surface receptors such as TNFR family death receptors, the intrinsic Bcl-2 family members and some other intracellular molecules like p53, MDM2, IAP, and Smac. The advance in the high-throughput bio-technologies has greatly accelerated the progress of cancer drug discovery.     

In vitro Biological Effects of Sulforaphane (SFN), Epigallocatechin-3-gallate (EGCG), and Curcumin on Breast Cancer Cells: A Systematic Review of the Literature

Much of the recent research in neoplasia has been focusing on the epigenetics of cancer cells, particularly as regards the search for potential molecular biomarkers that could be used for early diagnosis, effective treatment, and prognosis of several types of cancer. Carcinogenesis often starts with mutations in oncogenes and tumor suppressor genes, and it leads to anomalies in cellular processes as vital as cell cycle regulation and apoptosis. Because malignant changes arise as a result of genetic as well as epigenetic mechanisms, one possible means of intervention involves reprogramming gene expression, so as to—at least in part—revert the molecular alterations. DNA methylation and demethylation, acetylation and deacetylation of histones, and microRNAs are a few examples of the epigenetic mechanisms responsible for tumor development and progression. Many biologically active compounds present in food—including sulforaphane, curcumin, and epigallocatechin—have been found to modulate those processes. We here systematically review information on the effects of such bioactive dietary compounds on human breast cancer cell lines, and explore the mechanisms underlying those effects with a view to their potential therapeutic application.     

Rhodiola crenulata induces death and inhibits growth of breast cancer cell lines

Diverse compounds from many different chemical classes are currently targeted in preclinical analyses for their ability to act as both chemopreventive and chemotherapeutic agents. Phenolic phytochemicals from Rhodiola crenulata has such potential. This Rhodiola species is a perennial plant that grows in the Tundra, Siberia, and high-elevation regions of Tibet. The phenolic secondary metabolites isolated from R. crenulata were recently analyzed in a preclinical setting for their ability to treat lymphosarcomas and superficial bladder cancers. However, the effects of R. crenulata have yet to be examined for its implications in breast cancer prevention or for its chemotherapeutic abilities. Therefore this study investigated the effects of R. crenulata on breast cancer both in vivo and in vitro. Experiments using aggressive human-derived MDA-MB-231 and mouse-derived V14 breast cancer cell lines demonstrated that phenolic-enriched R. crenulata extract was capable of inhibiting the proliferation, motility, and invasion of these cells. In addition, the extracts induced autophagic-like vesicles in all cell lines, eventually leading to death of the tumor cell lines but not the immortal or normal human mammary epithelial cells. Finally, an in vivo experiment showed that phenolic-enriched dietary R. crenulata is effective in preventing the initiation of tumors and slowing down the tumor growth in mice bearing tumor grafts, thereby further demonstrating its possible potential for treatment of breast cancer progression and metastasis.     

Ganoderma lucidum (Reishi) Inhibits Cancer Cell Growth and Expression of Key Molecules in Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell–cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against cancer cells. We report the effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in IBC cells (SUM-149). Results show that Reishi selectively inhibits cancer cell viability although it does not affect the viability of noncancerous mammary epithelial cells. Apoptosis induction is consistent with decreased cell viability. Reishi inhibits cell invasion and disrupts the cell spheroids that are characteristic of the IBC invasive pathology. Reishi decreases the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP-9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL, E-cadherin, eIF4G, p120-catenin, and c-Myc protein expression and gelatinase activity. These findings suggest that Reishi is an effective anti-IBC therapeutic.