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1.
晚期肾透明细胞癌(renal clear-cell carcinoma)的预后不良,而且临床缺乏有效的治疗手段。随着人们对其分子生物学更加深刻的认识和分子靶向药物如受体酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)的出现,使晚期肾透明细胞癌临床治疗取得明显的进展。 相似文献
2.
Pfizer公司的口服抗癌药Sutent(sunitinib malate)用于胰岛细胞癌的噩期临床试验取得成功对英国NICE和欧洲泌尿科学学会(EAU)把它作为有低或中度风险的转移性肾细胞癌(mRCC)病人的首选一线酪氨酸激酶抑制剂产生有利作用。 相似文献
3.
肺动脉高压(PAH)以肺小动脉增殖和重塑为特征,患者肺血管阻力进行性增加,右心室后负荷增加,最终导致右心衰竭.大部分PAH患者疾病进展快,长期预后差.本文综述前列环素受体激动剂、可溶性鸟苷酸环化酶激动剂、酪氨酸激酶抑制剂和Rho激酶抑制剂等几类靶向治疗药物潜力品种的最新临床评价研究. 相似文献
4.
肾细胞癌占全部肾肿瘤的85%.美国癌症协会估计2007年将有新诊断肾癌患者51190例,其中40%在诊断时已经是晚期或进展期.美国FDA已于2007年5月批准rorisel(Temsirolimus)上市,用于治疗晚期肾细胞癌(RCC).该药是惟一上市的特异性抑制mTOR激酶的药物,是第一个治疗肾癌的靶向治疗药物,也是目前第一剂用于治疗癌症的注射剂. 相似文献
5.
分子靶向治疗药物已被用于治疗各种难治性癌症,然而其临床相关的心脏毒性给医生与患者带来了巨大的挑战。目前对临床常用的靶向治疗药物包括酪氨酸激酶抑制剂、免疫检查点抑制剂以及细胞治疗产品等所致心脏毒性的研究仍处于探索阶段,本文综述肿瘤靶向治疗药物所致心脏毒性的最新进展,并就当前抗肿瘤药的临床前评价进行讨论。 相似文献
6.
目的:了解实体瘤靶向药物的研究进展。方法:查阅近年来国内外相关文献,就实体瘤靶向药物的研究进行归纳和总结。结果:临床的实体瘤靶向药物主要分为单克隆抗体和酪氨酸激酶抑制剂(TKI)。单克隆抗体中的曲妥珠单抗针对乳腺癌能选择性与内表皮生长因子2(HER-2)基因调控的p185糖蛋白结合,阻滞表皮细胞生长因子与HER-2再结合,延缓癌细胞生长,但对心脏功能有一定影响;贝伐单抗通过特异性结合并阻滞血管内皮生长因子,抑制肿瘤血管生成,是用于晚期结直肠癌一线药物,辅助用于晚期结直肠癌、肺癌、卵巢癌的疗效均较好;帕尼单抗用于转移性结直肠癌,但易出现较严重的不良反应;凡德他尼用于甲状腺髓样癌;阿帕西普用于转移性结直肠癌,但应警惕其引起的严重不良反应;舍瑞替尼是治疗间变性淋巴瘤激酶阳性的晚期非小细胞肺癌(NSCLC)的高效靶向药物。TKI中的克唑替尼用于NSCLC患者疗效较好;维罗非尼用于黑色素瘤;维莫德吉用于晚期基底细胞癌;瑞戈非尼用于转移性结直肠癌;阿西替尼用于其他药物治疗无效的晚期肾细胞癌患者;卡博替尼用于不可手术切除的晚期局部或转移性甲状腺髓样癌。结论:靶向药物治疗实体瘤取得显著疗效的同时,其暴露的问题也在增多,需要开展大量的研究来推动和完善实体瘤的个体化、靶向治疗,提高其治疗效果和安全性。 相似文献
7.
原发性肝细胞癌(简称肝癌)是临床常见的恶性肿瘤之一,具有发病率高、预后差、死亡率高的特点,其发病率和死亡率均在全球恶性肿瘤中的排名前列。肝癌的高度异质性影响肿瘤的进展及治疗反应。由于大多数肝癌患者确诊已是晚期,系统治疗成为主要的治疗选择。索拉非尼是2007年推出的第一种多激酶抑制剂,且是之后十多年来唯一可供肝癌患者选择的靶向药物。直到2017年,另一种多激酶抑制剂仑伐替尼获批肝癌一线系统治疗。此外,免疫检查点抑制剂(ICIs)已经成为许多实体肿瘤(包括肝癌)有效的治疗方法。多项大型临床试验研究表明这些ICIs已被证明在治疗晚期HCC方面具有疗效。目前,许多晚期肝癌的临床试验正在进行中,这将给晚期肝癌患者的治疗带来持续的变化,并提高患者的生存率。本文总结了目前肝癌系统治疗的主要药物,讨论了目前在临床试验中的潜在药物可能,并讨论了今后肝癌系统治疗的发展方向。 相似文献
8.
表皮生长因子受体(EGFR)在非小细胞肺癌、黏液高分泌、肺纤维化等一系列肺部疾病中起着重要的作用,为肺部疾病治疗的新靶点.EGFR靶向药物主要有小分子酪氨酸激酶抑制剂(TKI)及抗EGFR单克隆抗体.本文综述目前处于临床研发阶段的新型EGFR靶向药物如不可逆TKI和下游信号通路蛋白抑制剂等,相关药物开发有望解决临床EG... 相似文献
9.
肝细胞癌是常见的恶性肿瘤之一,致死率很高.现有的手术切除、化疗、放射治疗等治疗方法,各具优势,但都存在适用范围有限、选择性不佳等问题.本文简要综述肝细胞癌的分子靶向治疗药物开发进展. 相似文献
10.
酪氨酸激酶抑制剂(TKI)作为一种小分子靶向药物,对肾癌患者疗效显著,但其药动学、药效学个体间差异较大,部分患者受疗效不佳甚至严重不良反应的困扰。该文介绍了索拉非尼、舒尼替尼、培唑帕尼、阿昔替尼4种TKI药物及临床应用,对其血药浓度、基因多态性与疗效个体间差异的关系做一综述,以期为4种TKI药物的临床应用提供参考。 相似文献
11.
Renal cell carcinoma (RCC) still represents a therapeutic challenge when patients have advanced or metastatic disease. Treatment using IL-2 and IFN-α continues to be the standard of care in patients who are able to tolerate such regimens. Targeted therapy may become the first-line treatment for patients resistant or intolerant to cytokines as new emerging drugs continue to be investigated. Understanding the genetic abnormalities related to the development of RCC (e.g., VHL gene abnormalities) and identifying molecular targets (e.g., epidermal growth factor, vascular endothelial growth factor and carbonic anhydrase IX) are playing a major role in the emergence of these novel agents for the treatment of this malignancy. Overall, these drugs are better tolerated and more acceptable to use by patients than the traditional cytokine-based regimens. The use of oral drugs to treat various malignancies including RCC seems to be the new paradigm of the future. Further understanding of their mechanisms of action and confirmation of their benefits on the clinical outcome is needed. 相似文献
12.
Background: The approval of sunitinib, sorafenib and temsirolimus has dramatically altered the management of renal cell carcinoma (RCC). Bevacizumab plus IFN may also be added to the therapeutic armamentarium. Axitinib (AG-013736) is an oral and selective tyrosine kinase inhibitor. Objective: Data supporting the development of axitinib for RCC are reviewed. Methods: Preclinical and clinical data available for axitinib for RCC are presented. Results: Axitinib inhibits VEGFR-1, VEGFR-2 and VEGFR-3 with picomolar potencies, and PDGFR-α, PDGFR-β and c-kit with nanomolar potencies. Phase II clinical trials of axitinib in pretreated RCC following sorafenib or cytokine treatment have demonstrated promising activity accompanied by a favorable toxicity profile. Further development of axitinib for RCC is warranted. 相似文献
13.
Background: The recent approvals of sunitinib, sorafenib and temsirolimus have revolutionized the management of renal cell carcinoma (RCC). Pazopanib (GW-786034) is a second-generation multitargeted tyrosine kinase inhibitor against VEGFR-1, 2 and 3, platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β and c-kit. Objective: Data supporting the development of pazopanib for RCC are reviewed. Methods: Preclinical and clinical data available for pazopanib are presented. Results: Preclinical evaluation has revealed excellent anti-angiogenic and anti-tumor activity in several mouse models. A Phase II clinical trial of pazopanib in untreated or cytokine/bevacizumab pretreated RCC has demonstrated promising activity accompanied by a favorable toxicity profile. A placebo-controlled Phase III trial is ongoing in untreated or cytokine-treated patients with RCC. Ongoing trials are further evaluating pazopanib in a variety of other malignancies. 相似文献
14.
肾细胞癌(RCC)是恶性度极高的泌尿系统肿瘤,早期病例主要以根治性切除为主,但进展性和转移性RCC的临床治疗效果不佳。随着分子生物学研究的进展,近期RCC靶向治疗不断取得新突破,本文综述进展性透明细胞癌和不同病理分型非透明细胞癌的分子发病基础及近年靶向治疗新进展。 相似文献
15.
Introduction: Over the past decade metastatic renal cell carcinoma (RCC) treatment landscape has dramatically evolved from the era of cytokines-based immunotherapy (which benefited very few patients, at the expenses of high toxicities) to the present era of targeted agents and novel immunotherapeutics, greatly improving the prognosis of our patients. Areas covered: Here we have reviewed the present status of the medical treatment of metastatic RCC. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for the relevant trials coducted so far. Expert opinion: Despite all the advances made in these relatively few years, further improvements are needed, since none of the available agents proved able to cure even a sigle metastatic RCC patient. In particular, advances are awaited from the results of ongoing trial of combinations of different immune checkpoint inhibitors and of immune checkpoint inhibitors with anti-VEGF/VEGFRs agents. Furthermore, a better understanding of the molecular escape pathways used by the tumor to overcome VEGFR blockade or immune activation will hopefully bring soon to the clinic more active, tailored treatments, to be used in second line and beyond. 相似文献
16.
Introduction: Metastatic Renal Cell Carcinoma (mRCC) was historically treated with cytokine therapy with a poor outcome. In the last decade, new therapies targeting vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin (m-TOR) pathways demonstrated efficacy in mRCC. Protein kinase inhibitors as well as monoclonal antibodies targeting these pathways have become the standard treatment of renal cell carcinoma (RCC) in the first-line setting and beyond. Areas covered: This review describes the various Phase III trials concerning protein kinase inhibitors including anti-angiogenic tyrosine kinase inhibitors (TKIs) and m-TOR serine/threonine kinase inhibitors, which have demonstrated a benefit in the treatment of mRCC. It focuses on efficacy, safety and management. Expert opinion: VEGF TKI and m-TOR inhibitors have significantly improved the outcome of mRCC and offer a gain in survival by sequential treatments for the majority of patients. But they induce a particular toxicity profile. An adequate management of each drug and its sequence in treatment is essential to optimise the outcome and preserve the quality of life (QoL) of patients with mRCC. In forthcoming years, pending results should indicate whether VEGF TKI are of interest in an adjuvant setting and if new drugs targeting will challenge the current standard guidelines in the metastatic setting. 相似文献
17.
Introduction: The aim of treatment in metastatic renal cell carcinoma is palliation. In the last 5 years, multiple targeted agents have been developed which have resulted in prolongation of patients' lives, but complete responses remain rare. New therapies and approaches are required to further improve the prognosis for patients with this disease. Areas covered: This review discusses the molecular targets in renal cell carcinoma relevant to the development of new treatments and describes the progress of novel therapies. The evidence is compiled from the PubMed database and proceedings of scientific meetings, searched up to December 2010. Expert opinion: A multitude of experimental agents are in clinical development and offer theoretical advantages over those currently in use. It is hoped that these treatments will result in better long-term control of metastatic renal cell carcinoma, with improved side effect profiles, but curative treatment in this disease remains elusive until the mechanisms underlying response and resistance to therapy are elucidated. Progress in the field has been limited by inadequate tissue collection within clinical trials; current and future clinical trial design will incorporate a larger translational component in an attempt to establish predictive biomarkers. 相似文献
18.
Hypoxia-regulated genes such as vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are both important for tumour progression in renal cell carcinoma (RCC). Drugs that block these and other pathways have been examined in Phase I and II clinical trials in patients with advanced or metastatic RCC. Results from a randomised study of an anti-VEGF antibody demonstrate a delay in the time to disease progression, suggesting a biological effect and change in the natural history of the disease. Results using small-molecule inhibitors of VEGF, FLT3, KIT and platelet-derived growth factor receptor tyrosine kinases, such as sunitinib, show a 40% objective response rate. Results from a Phase III clinical trial with sorafenib, an inhibitor of multiple tyrosine kinases, show only a 2% response rate; however, a statistically significant improvement in progression-free survival was observed. Objective responses have also been noted using an inhibitor of the mammalian target of rapamycin. Conversely, EGF receptor inhibitors, proteosome inhibitors, microtubule stabilising agents, cell-cycle inhibitors and imatinib were also examined with few objective responses. Ultimately, identifying the predictive factors for responsiveness to these targeted therapies may improve the clinical benefit; for example, RCC with biallelic mutations in the von Hippel-Lindau gene would have higher levels of hypoxia-inducible factor-1α, and may be more responsive to inhibitors of angiogenesis. Phase III studies comparing the combinations of targeted therapy could lead to a new standard of care for RCC. 相似文献
19.
Introduction: Locally advanced or metastatic renal cell carcinoma (RCC) is notoriously chemo- and radioresistant, leaving immunotherapy as the only treatment option. In recent years, targeted therapies have offered significant increases in progression-free survival (PFS). Despite this, the majority of patients soon develops resistant disease and finally succumbs. The need to implement treatment strategies that improve overall survival while having an acceptable safety profile is imperative. Areas covered: This review provides information on the efficacy of recently studied treatment strategies for advanced RCC. These include sequential and combination therapy of established drugs as well as data on agents in early clinical development. The Medline and ASCO database were searched for clinical trials on medical therapy of advanced RCC from 2004 until May 2010. Data on targeted therapies, including tyrosine kinase inhibitors, vascular endothelial growth factor inhibitors, mammalian target of rapamycin inhibitors, and antiepidermal growth factor receptor agents are summarized. Expert opinion: Improvements in response rates and PFS in patients with advanced RCC have been observed with new treatment strategies. The benefit in overall survival is less clear and needs further evaluation. Toxicity represents a concern especially in combination regiments. 相似文献
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