非小细胞肺癌分子靶向治疗标志物研究进展

肿瘤分子靶向治疗是指以肿瘤发生发展相关的关键分子作为靶点，利用抑制剂、阻断剂、抗体等药物进行抗肿瘤治疗的手段。分子靶向治疗具有特异性强、副作用小等特点，已成为非小细胞肺癌（non-small cell lung cancer，NSCLC）治疗领域的研究热点之一。目前针对NSCLC已上市的分子靶向药物主要包括癌基因分子靶向药物、抗血管生成药物、免疫靶向治疗药物以及多靶点抑制剂等。本文主要阐述不同分子靶向药物的作用机制、疗效及获益人群。     

癌症靶向治疗和免疫治疗的新进展学习班会议通知

靶向治疗以特异的分子为靶点,如BCR-ABL、EGFR、BRAF、KIT、HER2和ALK,已产生令人惊奇的疗效,但是肿瘤消退后由于出现耐药变异,癌症会逐渐进展。与靶向治疗进展的同时,最近研究sipuleucel-T和ipilimumab的三期临床试验取得成功,免疫治疗也可以延长癌症患者的生存时间,而且部分患者达到持久获益。提示免疫治疗时代已经到来。     

线粒体DNA在消化系恶性肿瘤发生发展中的作用机制研究进展

线粒体DNA（mt-DNA）是核外遗传信息的重要载体。近期研究结果显示,mt-DNA与多种恶性肿瘤的发生、转移密切相关,且可用于癌症的早期诊断和靶向治疗。因此进一步研究mt-DNA在消化系恶性肿瘤中的作用机制,对于筛选和鉴定肿瘤分子标志物用于抗肿瘤药物靶点、癌症诊断及预后分析均有重要的临床意义。本文对近年mt-DNA与消化系恶性肿瘤的潜在联系、临床应用及治疗靶点的研究进展进行综述。     

癌症靶向治疗和免疫治疗的新进展学习班会议通知

靶向治疗以特异的分子为靶点,如BCR-ABL、EGFR、BRAF、KIT、HER2和ALK,已产生令人惊奇的疗效,但是肿瘤消退后由于出现耐药变异,癌症会逐渐进展。与靶向治疗进展的同时,最近研究sipuleucel-T和ipilimumab的三期临床试验取得成功,免疫治疗也可以延长癌症患者的生存时间,而且部分患者达到持久获益。提示免疫治疗时代已经到来。     

信息博览

端粒酶与靶向治疗癌症靶向治疗因其巨大的优越性而有非常广阔的发展前景,而端粒酶作为肿瘤组织生长的标志性酶是癌症靶向治疗的重要靶点之一。由于端粒酶在肿瘤组织中特异性表达,使其在多种肿瘤的治疗中都可以发挥作用。而端粒酶细胞表面抗原的存在,使其与免疫治疗紧密的联系起来,也为针对端粒酶的癌症靶向治疗提供了更广阔的发展空间。随着研究的深入,多种端粒酶疫苗已进     

肿瘤恶病质治疗潜在分子靶点的研究进展

肿瘤恶病质是各种恶性肿瘤患者的主要并发症,常出现于肿瘤晚期,主要表现为患者体重丢失、贫血、代谢失衡及全身性器官衰竭,导致癌症患者生活质量下降,肿瘤化疗治疗效果被严重削弱,是众多癌症患者死亡的主要原因。目前,肿瘤恶病质治疗尚缺乏有效的特异针对性药物,但随着对肿瘤恶病质发生分子机制的深入研究,多个新的恶病质治疗潜在分子靶点被提出,为开发新的靶向治疗药物提供了可能。全文综述了抗肿瘤恶病质导致的肌肉减少以及脂肪降解的新分子靶点,并分类阐述其分子机制以及相关体内外实验研究成果,收集针对这些靶点的药物研究的现状,希望能为肿瘤恶病质新药开发及治疗提供研究思路和方向。     

中国乳腺癌免疫治疗转化研究进展

乳腺癌作为全球女性发病率最高的癌症,虽然辅助化疗、放疗、靶向治疗、内分泌治疗的使用已显著降低了患者的死亡风险,但仍有部分患者尤其是晚期患者无法从现有的治疗手段中获益。随着免疫治疗的不断发展,近年来中国的乳腺癌免疫治疗转化研究从基础到临床,从分子靶点、药物研发到临床试验,均取得了突破性的进展。本文将就中国乳腺癌免疫治疗转化研究中的治疗靶点、预测标志物、治疗手段等进行综述。      

肿瘤靶向治疗的现状和展望

攻克癌症一直是医学界面临的重大挑战。尽管对癌症的基因组学及表观遗传学进行了大量研究，在肿瘤的基因突变、表达谱及信号转导基础研究领域取得了重大进展，但在临床上，自从50年前Burchenal等开创癌症化疗以来，癌症患者的生存期并未见显著增长。近年来，针对肿瘤细胞受体、关键基因和调控分子为靶点的新型治疗方案已逐步从实验室走向临床，这种特异性杀灭肿瘤细胞的肿瘤靶向治疗（targeted therapy）已对癌症的分子分型、疗效及预后产生重大影响。为此，2006年5月美国Science作专题报道，认为这是癌症研究的新时代。本文根据国际上的最新学术观点，结合我们的研究成果，对肿瘤靶向治疗提出自己一些肤浅思考。     

推动创新研发,提升诊治能力!

什么叫肿瘤的分子靶向药物治疗(靶向治疗)?肿瘤的靶向治疗全称是分子靶向药物治疗,顾名思义,就是使合适的抗癌药物瞄准癌细胞上的分子靶点,'精确打击',实施杀伤癌细胞的独特治疗。这种靶点仅存在于癌细胞,是指在分子水平对癌细胞生存繁衍起重要作用的特定的蛋白分子、基因或通路,这个分子靶点可能是一个,更可能是多个。靶向药物就是针对这些靶点,对肿瘤细胞本身或其诱导的微环境进行特异性干预,使癌细胞死亡或失去功能。     

晚期肾癌靶向治疗的作用机制 耐药机制与对策

随着对肾癌发生、发展过程中分子调控机制研究的不断深入,以分子信号通路中的关键蛋白酶/ 蛋白作为靶点开发靶向药物,较好地改善了晚期肾癌患者的治疗现状。但是靶向药物在治疗过程中常出现耐药,从而导致治疗效果降低。本文将对肾癌靶向治疗的作用机制、耐药机制与对策作简要综述。     

Engineering antibodies for clinical applications in cancer.

The 'magic bullet' concept predicted over a century ago that antibodies would be used to target cancer therapy. Since then initial problems that were related to specificity, purity and immungenicity of antibody-based reagents have slowly been overcome due to developments in technology and increased knowledge. As a result, antibodies are in use for many clinical applications and now comprise the second largest category of medicines in clinical development after vaccines. For antibody-based cancer therapeutics the last 20 years have met with an explosion of knowledge about the biology of the disease and potential targets as well as new technology which allows cloning and manipulation of multifunctional antibody-based molecules. However, the focus still remains on developing therapeutics that will have potential for treating cancer in people and this is efficiently assessed in mechanistic clinical trials that feed back to the laboratory for further development. This review illustrates the mechanistic approach to making new molecules for antibody imaging and therapy of cancer. It is illustrated by examples of radioimmunotherapy and antibody-directed enzyme prodrug therapy developed by the authors.     

胰腺癌:靶向治疗的前景

Pancreatic cancer is a devastating disease characterized by almost identical incidence and mortality rates. Since this tumour is mostly diagnosed in an advanced stage there is usually no option for a curative surgical resection. In addition, pancreatic cancers known to be resistant to conventional treatment modalities such as chemotherapy and radiotherapy. Therefore, novel strategies for targeting these tumors are urgently needed. The increasing knowledge on the underlying pathogenetic mechanisms has led to the identification of surface receptor molecules that initiate intracellular signalling cascades upon ligand binding, thus leading to tumor progression. Targeting these receptors or their secreted ligands is therefore an attractive new approach for cancer therapy. The epidermal growth factor receptor （EGFR） and the vascular endothelial growth factor receptor （VEGFR） are transmembrane tyrosine kinase receptors which can be targeted by various compounds such as antibodies or small molecule inhibitors. In addition, various molecules targeting proteins secreted by pancreatic cancers such as matrix metalloproteinases （MMP＇s） or intracellular oncogenic signalling components such as the farnesyltransferase have been proposed as potential new approaches for targeted cancer therapy. The use of these agents alone or in combination with conventional therapeutic regimens is currently being evaluated and shows first promising results for pancreatic cancer therapy.     

The Outlook for Immune Checkpoint Targeting Strategies in Colorectal Cancer

Encouraging clinical activity for checkpoint blockade in melanoma, lung cancer, and a growing list of other malignancies has supported enthusiasm for testing this strategy in colorectal cancer. Although frequent observations of T cell infiltration into colorectal cancer and a well-established list of target antigens suggest colorectal cancer should be amenable to this approach, there was limited clinical evidence until recent demonstration of substantial activity for anti-PD-1 antibody therapy in microsatellite instability high colorectal cancers. Addition of other therapeutic modalities such as targeted therapy, other checkpoint molecules, or other immunotherapies to anti-PD-1 antibodies is currently under evaluation with the hope that it will expand the possible spectrum of colorectal cancers treatable with checkpoint blockade.     

Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules.     

Vector-mediated cancer gene therapy: an overview

In recent years there has been a dramatic increase in developing gene therapy approaches for the treatment of cancer. The two events that have permitted the formulation of concept of cancer gene therapy are the new understanding of the molecular mechanisms underlying oncogenesis, and the development of the DNA-delivery vehicles or vectors. Many approaches to cancer gene therapy have been proposed, and several viral and non-viral vectors have been utilized. The purpose of this review article is to describe the various strategies of cancer gene therapy (transfer of tumor suppressor genes, suicide genes-enzyme/pro-drug approach, inhibition of dominant oncogenes, immunomodulation approaches, expression of molecules that affect angiogenesis, tumor invasion and metastasis, chemosensitization and radiosensitization approaches, and chemoprotection of stem cells). The chapter also reviews the commonly used vectors (retroviral vectors, adenoviral vectors, adeno-associated viral vectors, pox viruses, herpes simplex viruses, HIV- vectors, non-viral vectors and targetable vectors) for cancer gene therapy. Some of the important issues in cancer gene therapy, and the potential future directions are also being discussed.     

Angiogenic molecules and mechanisms in breast cancer

One of the most promising and exciting anti-cancer strategies is one that is based on the inhibition of angiogenesis. Unlike conventional therapeutic approaches, anti-angiogenic therapy holds the unique promise of treating the disease in the absence of cytotoxicity or drug resistance. The link between angiogenesis and the progression of human breast cancer has been known for over 25 years, yet it is only in recent years, as endogenous stimulators and inhibitors of angiogenesis have been discovered and studied, that the promise of this therapeutic approach for breast cancer has come to be appreciated. This article presents a concise review of recent studies focused on the molecules and mechanisms that are related to the role of angiogenesis in breast cancer.     

Current screening for molecular target therapy of cancer

Recent progress in molecular biology and cancer biology has revealed that many molecules, which are heavily involved in the un-limited growth, anti-apoptotic effects and invasion of tumors, would be targets of cancer therapy. Part of the drugs which inhibit these molecules have shown clinical response as well as clinical benefits. In this review article, the summary of mechanism based drug screening for cancer as well as recent status of new molecular target drugs for cancer, are described.     

Targeting insulin-like growth factor pathways

Some cancer cells depend on the function of specific molecules for their growth, survival, and metastatic potential. Targeting of these critical molecules has arguably been the best therapy for cancer as demonstrated by the success of tamoxifen and trastuzumab in breast cancer. This review will evaluate the type I IGF receptor (IGF-IR) as a potential target for cancer therapy. As new drugs come forward targeting this receptor system, several issues will need to be addressed in the early clinical trials using these agents.     

Circular dumbbell miR-34a-3p and −5p suppresses pancreatic tumor cell-induced angiogenesis and activates macrophages

Angiogenesis is a tightly regulated biological process by which new blood vessels are formed from pre-existing blood vessels. This process is also critical in diseases such as cancer. Therefore, angiogenesis has been explored as a drug target for cancer therapy. The future of effective anti-angiogenic therapy lies in the intelligent combination of multiple targeting agents with novel modes of delivery to maximize therapeutic effects. Therefore, a novel approach is proposed that utilizes dumbbell RNA (dbRNA) to target pathological angiogenesis by simultaneously targeting multiple molecules and processes that contribute to angiogenesis. In the present study, a plasmid expressing miR-34a-3p and −5p dbRNA (db34a) was constructed using the permuted intron-exon method. A simple protocol to purify dbRNA from bacterial culture with high purity was also developed by modification of the RNASwift method. To test the efficacy of db34a, pancreatic cancer cell lines PANC-1 and MIA PaCa-2 were used. Functional validation of the effect of db34a on angiogenesis was performed on human umbilical vein endothelial cells using a tube formation assay, in which cells transfected with db34a exhibited a significant reduction in tube formation compared with cells transfected with scrambled dbRNA. These results were further validated in vivo using a zebrafish angiogenesis model. In conclusion, the present study demonstrates an approach for blocking angiogenesis using db34a. The data also show that this approach may be used to targeting multiple molecules and pathways.     

Targeted photodynamic therapy with multiply-loaded recombinant antibody fragments

Current photodynamic therapy (PDT) of cancer is limited by inefficiencies involved in specifically targeting photosensitizers to tumors. Although antibodies are being explored as targeting vehicles, they present significant challenges, particularly in terms of pharmacokinetics and drug-coupling. We describe here a novel and effective system to covalently attach multiple photosensitizer molecules (both preclinical, pyropheophorbide-a and clinically approved, verteporfin photosensitizers) to single-chain Fvs. Further, we demonstrate that not only do the resulting photoimmunoconjugates retain photophysical functionality, they are more potent than either free photosensitizer, effectively killing tumor cells in vitro and in vivo. For example, treatment of human breast cancer xenografts with a photoimmunoconjugate comprising an anti-HER-2 scFv linked to 8-10 molecules of pyropheophorbide-a leads to significant tumor regression. These results give an insight into the important features that make scFvs good carriers for PDT drugs and provide proof of concept of our unique approach to targeted photodynamic therapy (tPDT). This promises to significantly improve on current photodynamic therapies for the treatment of cancer.