抗肿瘤用药的应用及进展

新的抗肿瘤药物的研发目前已成为肿瘤治疗中的热点.对肿瘤细胞病理机制的日益深入探讨为抗肿瘤新药的开发提供了基础.目前在肿瘤治疗药物开发中新作用靶点的研究被重点推崇,这类药物被相继开发出来(如紫杉烷类).针对DNA小沟部位的药物如卡折来新等已经开始在临床应用.顺铂及其同类物在临床中应用较为广泛,最近对其机理的研究也取得了新的进展.JM 216由于具有与胞嘧啶类似的结构而容易被体内的DNA整合.在临床应用中其对非小细胞肺癌的抑制作用明显,但最适应用剂量及应用疗程的问题仍然没有得到解决.另外针对细胞信号转导通路的药物如蛋白激酶C抑制剂等在肿瘤治疗中的研究也成为新的热点.一些抗肿瘤老药的新用途也正在成为肿瘤治疗药物开发中的新关注对象.     

抗肿瘤药物的临床应用进展

本文综述和分析近年来抗肿瘤药物的临床应用现状和研究新进展,传统的细胞毒类药物包括烷化剂类药物、抗代谢类药物、金属铂类药物、抗肿瘤激素类药物和抗肿瘤抗生素等由于其使用价值在临床上仍享有一定的地位,不过因为其治疗的局限性以及不良反应的危害,新开发的药物、分子靶向药物和抗肿瘤植物药在某些领域正逐步取代其位置,成为治疗的首选。随着临床应用的不断发展,新的肿瘤治疗药物如海洋来源药物、抗肿瘤中草药等将在未来一段时间内得到进一步开发。     

基于表观遗传学的抗肿瘤药物研究进展

近年来,随着人类基因组计划的完成、绘制人类基因组甲基化可变位点图谱计划的展开、有关表观遗传学与肿瘤的发生发展及表观遗传治疗药物研究的深入,尤其是DNA甲基转移酶和组蛋白去乙酰化抑制剂等在肿瘤患者临床治疗的成功应用,表观遗传学逐渐成为肿瘤治疗研究的热点。本文综述了近年来基于表观遗传学的抗肿瘤药物药理学作用研究进展,以期为癌症的治疗和基础研究提供一些新的思路。     

小檗碱抗肿瘤作用机制的研究进展

小檗碱具有多种药理作用,其临床应用广泛。目前其抗肿瘤作用成为研究热点,可通过多种途径抑制肿瘤的发生及发展。该文就近年来国内外关于小檗碱抗肿瘤作用的相关研究进行综述,概括小檗碱对肿瘤的发生、抑制肿瘤细胞增殖、促进凋亡、诱导分化、抑制肿瘤细胞转移、协同化疗药物作用及增强放疗敏感性等方面的作用机制,为进一步研究小檗碱抗肿瘤作用及开发小檗碱新的药理作用提供依据。     

寻找以线粒体为靶点的抗癌新药

寻找肿瘤药物作用的新靶点和合成新的抗肿瘤药一直是肿瘤治疗研究的重大课题。线粒体结构和功能的改变，不仅会干扰肿瘤细胞的生长、代谢和增殖等过程，最终还会触发很多肿瘤细胞凋亡。随着线粒体调控细胞凋亡的发现，线粒体诱导肿瘤细胞凋亡成为目前研究的新热点。最近开发的一些抗肿瘤新药，能够直接作用于线粒体，而且还是克服肿瘤治疗过程中凋亡耐受的一种新策略。     

微管靶向药物抗肿瘤侵袭转移潜力研究进展

恶性肿瘤是一类严重危害人们生命和健康的重大疾病。目前,传统的抗肿瘤治疗在靶向性杀伤原发肿瘤细胞上展现出一定的优势,但针对肿瘤转移这一亟待解决的难题仍未有明显突破,因此,探索新型抗肿瘤转移药物对改善肿瘤的治疗效果具有重要意义。微管在真核细胞有丝分裂、信号转导、细胞器运输、细胞运动等多种生理过程中的重要作用,使其成为抗肿瘤药物的重要研究靶点。新近的研究证明,一些微管靶向药物（MTAs）不仅对肿瘤细胞具有抑制增殖、诱导凋亡的作用,还能在亚致死剂量下显著抑制肿瘤细胞的迁移与侵袭,这为解决此类药物的剂量限制性毒性提供了可能,从而使其更加有效地发挥抗肿瘤作用。本文就MTAs在抗肿瘤侵袭转移中的作用及相关机制的研究进展进行综述,旨在为开发MTAs在临床抗肿瘤治疗中新的应用潜能提供新思路。     

丹参酮在消化道肿瘤中的应用及研究现状

随着细胞生物学及分子生物学的研究进展，新的肿瘤治疗途径靶点不断被发现，新的治疗药物陆续被开发出来，高效低毒成为新方法、新药物的切入点。中药以其天然自然、毒副作用小的优势进入了人们的视野，也为中药抗肿瘤研究提供了新的思路及方法，其中丹参及其主要有效成分研究较多而备受瞩目。本文就近年来关于丹参在消化系肿瘤的应用及研究现状作一综述。     

抗肿瘤药物研究进展

目的:肿瘤(tumour)是指机体在各种致瘤因子作用下,局部组织细胞增生所形成的新生物(neogrowth),因为这种新生物多呈占位性块状突起,也称赘生物(neoplasm)。根据新生物的细胞特性及对机体的危害性程度,又将肿瘤分为良性肿瘤和恶性肿瘤两大类,而恶性肿瘤则成为日益常见且严重威胁人类生命和生活质量的主要疾病之一。方法:目前在中国乃至全世界,癌症已成了导致人类死亡的第二大原因。结果:随着对肿瘤特性和本质的研究,抗肿瘤药物正从传统的细胞毒药物向针对机制的多环节作用的新型抗肿瘤药物发展。目前抗肿瘤药物的发展已进入了一个新的时代,从天然植物药物的开发(如紫杉醇),已发展到基因治疗、免疫治疗以及新的靶点药物。结论:因此,在肿瘤的综合治疗中,各种药物的治疗手段已日益受到重视。     

功能化碳纳米管在肿瘤诊疗领域的研究进展

碳纳米管以其管状结构所具有的高载药量、易穿透细胞膜等特性成为了许多抗肿瘤药物和基因的优良载体,且随着对碳纳米管研究的逐渐深入,其在肿瘤光热治疗和肿瘤诊断方面的应用也成为了目前的研究热点。然而碳纳米管固有的化学惰性、易聚集等特性限制了其在临床上的应用,为克服其缺陷,研究者通常会先对碳纳米管进行功能化,再对功能化碳纳米管进行一系列的研究。本文对功能化碳纳米管在肿瘤化疗和基因治疗、肿瘤光热治疗以及肿瘤诊断方面的应用进行了总结。     

博莱霉素在恶性肿瘤中应用的研究进展

恶性肿瘤是世界范围内造成死亡的主要原因之一,发病率高且预后差。近年来,在分子生物学研究层面探讨药物与肿瘤的相互作用,开发新型的抗癌药物及药物的靶向治疗策略成为研究的新热点。博莱霉素(BLM)作为一种新型抗生素,可与肿瘤细胞DNA结合,干扰DNA的复制和转录,进而抑制肿瘤细胞的增殖和生长过程,达到肿瘤抑制的作用。在临床上主要与阿霉素等抗癌药物联合应用,对头颈部鳞癌、鼻咽癌、恶性淋巴瘤、食管癌、结肠癌、外阴癌、睾丸癌、肺癌、霍奇金病等均有良好的疗效。本文旨在阐述博莱霉素的分子结构和作用,为临床恶性肿瘤的治疗提供新的靶向药物和新思路,并对其在治疗恶性肿瘤中应用的研究进展及分子机制进行综述。     

基于DNA的纳米材料在肿瘤治疗领域的研究进展

肿瘤治疗药物通常存在水溶性差、靶向性低、稳定性差、不易被肿瘤细胞摄取等不足,开发一种理想的药物递送载体仍是肿瘤治疗领域亟待解决的重要问题。由于具有良好的序列可编程性、生物相容性和生物可降解性,基于DNA的纳米材料已被广泛用作肿瘤治疗的药物递送载体。大量研究表明,DNA纳米材料可以有效装载肿瘤治疗药物,实现肿瘤组织靶向递送、高效细胞摄取与刺激响应性药物释放。本文从DNA纳米技术的历史与发展入手,例举DNA纳米材料作为药物递送载体在化疗、基因治疗、免疫治疗和光动力疗法中的应用进展,并对其未来发展进行展望,以期为该领域其他研究工作者提供参考。     

乳腺癌靶向治疗新进展

近年来乳腺癌靶向治疗发展迅速,出现了许多新的药物和治疗靶点,包括新的抗HER-2药物,针对其他酪氨酸激酶如Src和其他信号转导通路如PI3K/Akt/mTOR的抑制剂。与此同时,多靶点联合治疗和单克隆抗体介导的免疫治疗的思路也逐渐得到认可。主要综述这些新药物的效果和临床应用前景,并对治疗新思路和面临的问题和挑战进行探讨。     

Timing of new black box warnings and withdrawals for prescription medications

CONTEXT: Recently approved drugs may be more likely to have unrecognized adverse drug reactions (ADRs) than established drugs, but no recent studies have examined how frequently postmarketing surveillance identifies important ADRs. OBJECTIVE: To determine the frequency and timing of discovery of new ADRs described in black box warnings or necessitating withdrawal of the drug from the market. DESIGN AND SETTING: Examination of the Physicians' Desk Reference for all new chemical entities approved by the US Food and Drug Administration between 1975 and 1999, and all drugs withdrawn from the market between 1975 and 2000 (with or without a prior black box warning). MAIN OUTCOME MEASURES: Frequency of and time to a new black box warning or drug withdrawal. RESULTS: A total of 548 new chemical entities were approved in 1975-1999; 56 (10.2%) acquired a new black box warning or were withdrawn. Forty-five drugs (8.2%) acquired 1 or more black box warnings and 16 (2.9%) were withdrawn from the market. In Kaplan-Meier analyses, the estimated probability of acquiring a new black box warning or being withdrawn from the market over 25 years was 20%. Eighty-one major changes to drug labeling in the Physicians' Desk Reference occurred including the addition of 1 or more black box warnings per drug, or drug withdrawal. In Kaplan-Meier analyses, half of these changes occurred within 7 years of drug introduction; half of the withdrawals occurred within 2 years. CONCLUSIONS: Serious ADRs commonly emerge after Food and Drug Administration approval. The safety of new agents cannot be known with certainty until a drug has been on the market for many years.     

Antiviral agents for influenza, hepatitis C and herpesvirus, enterovirus and rhinovirus infections

Advances in antiviral therapy have involved both development of new, effective drugs and modification of pre-existing drugs or regimens to increase effectiveness. New agents against influenza virus are the neuraminidase inhibitors zanamivir and oseltamivir, which target specific viral processes and have minimal side effects. New agents for herpesviruses (famciclovir, valaciclovir, valganciclovir) have greater oral bioavailability, allowing less frequent dosing, but mechanisms of action are similar to older agents (aciclovir, ganciclovir). Pleconaril has some activity against enteroviruses and is available for compassionate use in meningitis; it also shows some efficacy against rhinoviruses in ongoing trials, but is not available for routine clinical use. Hepatitis C treatment efficacy has improved dramatically with the introduction of combination interferon-ribavirin therapy, with sustained-response rates up to 60%.     

2011年美国FDA批准新药简析

2011年美国食品药品监督管理局（FDA）共批准30个新药。简要介绍其中的重点品种,并就新药研发的现状与趋势进行分析。在2011年FDA批准上市的新药中,有11个为首创一类新药,其中50余年来首次上市的系统性红斑狼疮治疗药物贝利单抗、30余年来首次获准上市的霍奇金淋巴瘤靶向治疗药物本图希单抗-维度汀、慢性丙型肝炎治疗药物特拉普韦和波塞普韦、肿瘤免疫治疗药物依普利单抗、基于基因学检测的肿瘤个体化治疗药物克唑替尼和维拉芬尼等药物作用独特或市场前景广阔,颇受关注。     

Research and Development of Neurological and Psychiatric Drugs Supported by National Science and Technology Major Project of “Major New Drugs R&D”

National Science and Technology Major Project of "Major New Drugs R&D" have made great achievements during nearly 10 years since it was launched in 2008. In major drug research and development, a batch of innovative drugs for treatment of major diseases which seriously endanger the health of our people, such as cancer, cardiovascular disease, inflammatory disease, bacterial and virus bacterial infection diseases, etc., have been successfully developed. On the other hand, a number of common clinical drugs have been reformed technically and the qualities of them are improved significantly, aiming at the requirements of clinical medication. The research and development of new drugs of neuropsychiatric diseases are one of the important field supported by "Major New Drugs R&D" project. Up to now, more that 180 new drug projects of neuropsychiatric diseases in different research and development stages have been supported by the project, and some of them have made significant progresses and show potential and good prospects for development. For example, Morinda officinalis oligosaccharides, an antidepressant, has been approved and available to the public. 971, a new drug for treatment of Alzheimer's disease, has completed phase III clinical trials and obtained very good and encouraging results. Orcinoside, an antidepressant, is undergoing Phase II clinical trials. The research of sustained-release microsphere of antipsychotic drug, risperidone, has made significant progress.
The period of the 13th Five-Year Plan is the final five years and final stage for implementation of "Major New Drugs R&D" Project. With the economic and social development, the demands of protecting health and improving people's livelihood are even greater and stronger. Thus, it is of great significance to implement "Major New Drugs R&D" Project better and faster. During the 13th Five-Year Plan, the project fully implements the innovation-driven development strategy, and further focuses on its purpose, emphasizes the key points and accelerates implementation according to the principle of focus development. Further more, the project focuses on new drug research and development and the related key technology studies, and strengthens the construction of innovation capabilities. The main tasks have been arranged according to the “Three Importance” principle which means research and development of major new drugs, meeting important needs and solving important problems, so that to make the aims and tasks of the project more focused and clearer. Next, the development strategy study of the14th Five-Year Plan for "Major New Drugs R&D" project will be initiated. The research and development of neuropsychiatric drugs would still be a major field in the project. On one hand, "Major New Drugs R&D" project would further advance of technological innovation and research innovative drugs. Meanwhile, based on long-term development, the project would support and strengthen the related basic research of neuropsychiatric disease, translate and apply the results of basic research to provide rich knowledge for new drugs research and development. On the other hand, fully taking advantage of traditional Chinese medicine to discover and develop new neuropsychiatric drugs from traditional Chinese medicine is of great significance with a broad application perspective.     

Remission-inducing drugs in rheumatoid arthritis

The administration of certain drugs to patients with established rheumatoid arthritis frequently results in improvement that is slow to appear but persists for long periods, even after the drug is discontinued. The three main drugs with this effect, whose efficacy and toxicity are reviewed in this paper, are gold salts, D-penicillamine and chloroquine. The cytotoxic agents used to treat rheumatoid arthritis, which likely have nonspecific anti-inflammatory actions and have serious long-term side effects, are also briefly reviewed. A new drug, levamisole, is currently being tested in patients with rheumatoid arthritis. It is suggested that the time for considering the introduction of a remission-inducing drug in patients with progressive rheumatoid arthritis is after an adequate trial of therapy with salicylates or other nonsteroidal anti-inflammatory agents, or both, and before the oral administration of steroids. It is difficult, however, on the basis of rigorous clinical comparisons, to recommend which of the three main remission-inducing drugs should be tried first, although gold salts have been used the most. Patients who have improved with 6 months of chrysotherapy may continue treatment for at least 3 years, during which time the frequency of mucocutaneous and renal toxic effects will steadily decrease. Some aspects of the medical economics of therapy with remission-inducing drugs for rheumatoid arthritis are discussed.     

New drugs for the treatment of epilepsy: a practical approach

The availability of new antiepileptic drugs has broadened the spectrum of medical treatment options in epilepsy. The new agents, together with established drugs, offer substantial choice for doctors treating patients with focal or generalised epilepsy. The newer antiepileptic drugs are not necessarily more effective but usually better tolerated than the traditional agents, mainly because of favourable pharmacokinetic profiles and fewer interactions. Because treatment options have increased, drug therapy can now be tailored to the requirements of individual patients. Nevertheless, significant safety and efficacy issues continue to exist and there is a need for the development of even better agents. This review describes the clinical use of the new antiepileptic drugs, but focuses in particular on monotherapy, the treatment of generalised seizures, teratogenicity, and the cognitive side effect profile of the newer compounds.     

非小细胞肺癌分子靶向治疗的毒性反应研究进展

近年来,非小细胞肺癌的分子靶向治疗成为研究的热点,分子靶向治疗药物主要包括表皮生长因子受体 (epidermal growth factor receptor,EGFR)单克隆抗体、血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)单克隆抗体、表皮生长因子受体酪氨酸激酶抑制剂等。这些药物在临床上都取得了一定的疗效,同时也出现了皮疹、腹泻、高血压等若干毒性反应,还有一些新药,如索拉非尼、舒尼替尼、伏立诺他、范得它尼等,都有相关的毒性反应。分子靶向治疗毒性反应严重影响了患者的生活质量和服药的依从性。本文就非小细胞肺癌分子靶向药物的毒性反应及处理措施作一综述。     

Precision medicine: Uses and challenges

Precision medicine has brought in many changes to the practise of medicine. The omics-based development of biomarkers and pharmaco-omics-based drug development programmes are evidences for the advancement. However, the field where it has proved to be most useful is in the development of various modalities of treatment in oncology. Various drugs targeting vascular endothelial growth factor, epidermal growth factor, tyrosine kinase receptor and rat sarcoma mutations have come to the forefront proving to be beneficial in many cancers. Some of the classic drugs developed using this concept include trastuzumab, bevacizumab, cetuximab and panitumumab among others. Precision medicine has been put to best use in the COVID-19 pandemic through use of various biomarkers such as IL-6 and c-reactive protein in assessing severity of disease, for development of various therapies and also to judge efficacy of vaccines. Precision medicine is also finding its place in management of infectious diseases, chronic diseases such as asthma, connective tissue diseases, cardiovascular diseases, diabetes and obesity. India has also made its presence felt in the field by launching various initiatives such as the Indian genome project and Indian cancer genome atlas. Numerous challenges still exist to the future of precision medicine such as cost involved, ethics, security of the Big data, merger of various platforms to integrate data and also availability of trained manpower to manage the data and algorithms. This new age medicine is a big step forward for mankind and hopefully it will bring more benefits for both patients and the caregivers in the near future.