靶向药物在肾细胞癌中的研究进展

肾细胞癌是泌尿系统常见的恶性肿瘤之一,起病隐匿,目前手术仍是肾细胞癌的唯一根治方法.近年来,随着靶向药物的问世,使得肾细胞癌治疗的有了更多的选择,尤其是针对进展型肾癌,另外,在肾细胞癌的辅助与新辅助治疗上也有不错的结果,现综述如下.     

肾细胞癌的靶向治疗药物研究现状

靶向治疗是转移性肾癌的一线及二线治疗手段,其药物从作用机制主要分为两类:血管内皮生长因子(VEGF)/血管内皮生长因子受体(VEGFR)和抑制mTOR途径.最近开发的药物,包括酪氨酸激酶抑制剂、单克隆抗体和mTOR抑制剂,能靶向作用于肾癌的酪氨酸激酶和细胞内通路,产生抗肿瘤作用.本文综述较有前景的靶向药物,包括舒尼替尼( Sunitinib)、索拉非尼(Sorafenib)、帕唑帕尼(pazopanib)、贝伐单抗(Bevacizumab)及替西罗莫司Temsirolimus.     

外科联合靶向治疗在肾细胞癌中的应用

肾细胞癌是肾脏恶性肿瘤最常见类型。本文就减瘤性肾切除术联合靶向治疗在mRCC中的应用;新辅助靶向治疗在局部进展性肾癌中的应用以及辅助靶向治疗在高危复发转移肾癌中的应用作一综述。     

树突状细胞疫苗在晚期肾细胞癌治疗中的研究进展

树突状细胞（DC）是目前发现强大的抗原提呈细胞（APC），能有效激发T细胞应答并诱导特异性细胞毒性T淋巴细胞（CTL）生成。肾癌是泌尿系常见的恶性肿瘤，发病率位于泌尿系肿瘤的第2位，其主要治疗方法是外科手术，化疗、放疗、激素治疗均不敏感。但是，由于肾癌是一种免疫原性很强的肿瘤，利用DC疫苗接种宿主、诱导或增强宿主防御功能、提高机体免疫系统对肿瘤的特异杀伤能力，已成为晚期肾癌免疫治疗中的研究热点。     

肾细胞癌靶向治疗预后相关因素研究进展

肾细胞癌（RCC）是泌尿系统常见的恶性肿瘤之一。分子靶向治疗是通过干预肿瘤细胞信号传导通路,抑制肿瘤的生长。相比于传统的细胞冈子治疗手段．肾癌靶向治疗效果更好。但是目前对肾癌靶向治疗的预后仍缺乏有效判断手段,本文结合最新研究综述了RCC靶向治疗预后密切相关的影响冈素研究现状及进展。     

遗传性肾细胞癌的研究进展

肾癌有遗传和散发两种形式,对肾癌发病机制的理解相当一部分来自对遗传性肾癌的研究.本文对von Hippel Lindau病、遗传性乳头状肾癌、Birt Hogg Dubé综合征、遗传性平滑肌瘤病肾细胞癌等遗传性肾细胞癌的研究进行了综述.     

肾细胞癌佐剂治疗研究进展

随着检测手段的不断完善,越来越多的肾细胞癌患者被临床发现．而传统的外科手术治疗并不能使所有患者取得良好疗效,化疗、放疗对其也不敏感,然而佐剂治疗作为一种新的治疗方法为肾细胞癌患者带来了新的希望。     

转移性肾细胞癌靶向药物治疗的现状

转移性肾细胞癌(metastatic renal cell carcinoma, mRCC)预后不良,而传统治疗方法对其疗效非常有限。而靶向治疗的诞生对于转移性肾细胞癌治疗具有革命性的意义,使得患者的生存周期大幅延长。本文就目前靶向治疗药物的原理、分类、疗效、药物耐受及对策等进行了总结。     

Molecular targeted therapy for renal cell carcinoma

Renal cell carcinoma (RCC) accounts for approximately 2% of all cancer cases worldwide. Metastatic disease is often present at the time of diagnosis of RCC and its poor response to chemotherapy and radiotherapy causes poor prognosis. Immunotherapy is relatively effective for RCC, but the response rate is approximately 15-20%. Therefore, new therapeutic approaches are necessary for these patients with metastatic RCC. Recently, the mechanisms responsible for the growth of RCC have been clarified, and molecular targeted therapy has been developed. In this paper, we review the new molecular targeted therapeutic agents effective for RCC.     

化疗及靶向药物治疗肉瘤样肾癌的Meta分析

目的 系统评价化疗及靶向药物治疗肉瘤样肾癌的有效性和安全性.方法 计算机检索PubMed、中国期刊全文数据库(CN KI)等,收集2000年1月～2013年12月国内外公开发表的有关化疗及靶向药物治疗肉瘤样肾癌的试验研究文献.根据Cochrane的质量评价标准评价,采用RevMan4.2软件进行统计学分析.结果 最终纳入5个文献,共128例患者.meta分析结果显示与化疗相比,靶向药物联合化疗不但显著提高了肉瘤样肾癌的疾病控制率(OR =2.11,95％ CI:1.30 ～2.61,P＜0.0001),还显著提高了有效率(OR =2.25,95％ CI:1.53 ～3.11,P＜0.0001).结论 与化疗相比,靶向药物联合化疗可进一步提高疗效,是肉瘤样肾癌较好的治疗方案.     

Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma

Background

The recent development of multiple targeted agents for metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm; hence the benefit and optimal timing of cytoreductive nephrectomy is being reevaluated.

Objective

To determine primary tumor response to treatment with targeted agents in patients with mRCC.

Design, setting, and participants

We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between November 2004 and December 2009 without prior systemic treatment who received targeted therapy with their primary tumor in situ.

Measurements

Two independent reviewers measured the diameter of primary and metastatic tumors at baseline and subsequent scans, using Response Evaluation Criteria Solid Tumors (RECIST) v.1.1 to assess disease response.

Results and limitations

We identified 168 consecutive patients with a median 15 mo of follow-up and a median maximum tumor diameter of 9.6 cm. Median maximum primary tumor response was −7.1% (interquartile range: −14.0 to −0.1).A total of 61 patients had multiple studies available for evaluation. In 43 patients with <10% decrease in primary tumor within in the first 60 d, median maximum response was −7.2% at 154 d versus −24.5% maximum response at 174.5 d for 18 patients with ≥10% decrease in primary tumor during the initial 60 d.

Conclusions

Decrease in primary tumor diameter >30% while on targeted therapy for mRCC is rare, with most patients demonstrating minimal or no decrease in primary tumor diameter. Early response predicts a better overall primary tumor response.     

Recent advances in targeted therapy for renal cell carcinoma

PURPOSE OF REVIEW: To provide an overview and summary of the recent developments in the use of targeted therapy in the management of advanced kidney cancer. The focus is on publications within the last year. RECENT FINDINGS: The last year has seen several exciting developments in the targeted approach to managing advanced renal cell carcinoma. The benefits of small-molecule tyrosine kinase inhibitors have been demonstrated in two large-scale, phase III prospective, randomized controlled trials. There is growing evidence, some not yet published, that mammalian target of rapamycin inhibitors are effective in this disease and the roles of therapies directed at the receptor for vascular endothelial growth factor continue to be refined. SUMMARY: Recent published trials offer substantial hope for those patients with advanced kidney cancer, where before the outlook was often bleak. There is an expanding menu of potential agents in this disease, so-called targeted therapies, that are grounded in a growing understanding of the biology of kidney cancer. Many challenges and questions still remain, but there are encouraging signs of progress and hope for the future.     

Consolidative surgery after targeted therapy for renal cell carcinoma

Renal cell carcinoma is the most lethal of the common genitourinary neoplasms, with 30% to 40% of patients eventually dying from disease progression. Although the recent development of targeted therapies against kidney cancer has yielded substantially improved tumor response rates and progression-free survival, these agents are still not curative. The integration of systemic therapies with surgery still represents the best management for select patients with advanced disease. Specifically, consolidative surgery may play a vital role in the management of this challenging patient population. However, concerns remain regarding the potential for increased surgical morbidity complicating the integration of surgery after targeted therapy. Careful patient selection and specific precautions to increase surgical safety should be implemented.     

Recent advances in molecular targeted therapy for metastatic renal cell carcinoma

Advanced renal cell carcinoma (RCC) is resistant to chemotherapy and radiotherapy. Immunotherapy is relatively effective against RCC. However, the response rate is approximately 15–20%. Therefore, new therapeutic approaches are necessary. Recently, molecular mechanisms responsible for the proliferation of RCC are identified, and molecular targeted therapy is developed. Bevacizumab, sorafenib, sunitinib, axitinib, temsirolimus, everolimus are promising molecular targeted therapeutic agents for metastatic RCC, and will be used widely in clinics in the near future. In addition, combination therapy with molecular targeted therapy and other therapies including immunotherapy may also be developed soon.     

Current status of targeted therapy for advanced renal cell carcinoma

The treatment of metastatic renal cell carcinoma (mRCC) has recently evolved from being predominantly cytokine-based treatment to the use of targeted agents, which include sorafenib, sunitinib, bevacizumab (plus interferon alpha [IFN-α]), temsirolimus, everolimus, pazopanib, and most recently, axitinib. Improved understanding of the molecular pathways implicated in the pathogenesis of RCC has led to the development of specific targeted therapies for treating the disease. In Korea, it has been 5 years since targeted therapy became available for mRCC. Thus, we now have broader and better therapeutic options at hand, leading to a significantly improved prognosis for patients with mRCC. However, the treatment of mRCC remains a challenge and a major health problem. Many questions remain on the efficacy of combination treatments and on the best methods for achieving complete remission. Additional studies are needed to optimize the use of these agents by identifying those patients who would most benefit and by elucidating the best means of delivering these agents, either in combination or as sequential single agents. Furthermore, numerous ongoing research activities aim at improving the benefits of the new compounds in the metastatic situation or their application in the early phase of the disease. This review introduces what is currently known regarding the fundamental biology that underlies clear cell RCC, summarizes the clinical evidence supporting the benefits of targeted agents in mRCC treatment, discusses survival endpoints used in pivotal clinical trials, and outlines future research directions.