进展期肾细胞癌的治疗进展

进展期肾细胞癌(RCC)的临床预后欠佳,由于其对于传统的放化疗的低敏感性,使得临床工作中缺乏较为有效的治疗手段.多个因素影响进展期肾癌的临床预后.目前免疫治疗可使部分进展期肾癌得到部分程度的缓解,新兴的靶向治疗在前期的临床实验中取得了令人满意的效果,使部分患者的肿瘤进展得以延迟,RCC靶向治疗制剂多针对RCC细胞增生、血管形成等多个靶向途径,包括Sorafenib,Sunitinib,Temsirolimus和Bevacizumab等.而联合免疫治疗,将对进展期肾癌的预后产生更为有效的改善.     

蛋白激酶B在肾细胞癌中表达及其功能的研究进展

肾细胞癌(renal cell caricinoma,RCC)作为最常见的肾脏恶性肿瘤,约占肾脏恶性肿瘤的90％.肾癌发病率近年来有上升趋势,早期肾癌患者可以通过手术达到良好的治疗效果,晚期患者由于缺乏有效的治疗手段,预后较差.靶向治疗是晚期肾癌的一线治疗方案,但长期的靶向治疗容易出现耐药以及带来副反应.因此,需要探索...     

转移性肾细胞癌分子靶向治疗的进展

肾细胞癌(renal cell carcinoma,RCC)约20%～30%发现时即有转移,此类患者预后很差,5年生存率＜10%[1].近年来随着对RCC分子机制研究的进展,新型分子靶向药物在临床实践中取得了显著疗效,现对转移性肾癌靶向治疗进展综述如下.     

肾癌的靶向治疗研究进展

进展期肾癌和转移性肾癌的预后差，系统治疗作用局限，分子靶向治疗是有希望的治疗手段。本文就肾癌靶向治疗的分子机制、临床试验及疗效等作一综述。     

肾透明细胞癌的细胞遗传学和分子遗传学研究新进展

肾癌(renal cell carcinoma,RCC)是泌尿系统常见恶性肿瘤之一,其中约80%为膺透明细胞癌(clear cell renal cell carcinoma,CCRCC).遗传学新技术的运用,促进了肾癌细胞遗传学和分子遗传学研究,初步确定了肾癌发生发展和预后相关的染色体及基因,对肾癌发生的信号通路也有了较深刻的认识.这为研究CCRCC的发生发展机制,寻求新的诊断和预后标志及治疗靶点提供理论基础.     

纳米材料在肾癌治疗中的研究进展

晚期肾癌(renal cell carcinoma,RCC)预后较差,靶向药物及免疫检查点抑制剂虽可使部分患者生存获益,但存在生物利用度差、非特异靶向性、药物相关副反应多等问题,同时长期治疗易产生耐药性,降低了治疗效果.纳米材料为近年肿瘤领域研究的热点,具有可控的表面化学活性、可控的药物释放动力学以及高渗透长滞留效应,...     

PI3k／Akt／mTOR信号转导通路与肾癌

进展期肾癌和转移性肾癌的预后差,生物治疗及放化疗作用局限,随着现代生物技术的发展,人们认识到PI3k／Akt／mTOR信号转导通路与细胞增殖和细胞凋亡有关,在肾癌的发生发展中起着重要作用。针对该通路的分子靶向药物在肾癌治疗的临床试验中起到了很好的疗效。本文针对PI3k／Akt／mTOR信号转导通路在肾癌靶向治疗中的相关研究作一综述。     

肾癌相关基因GYLZ-RCC18对肾癌细胞系GRC-1抗死亡作用机制的研究

目的：应用反义基因转染技术探讨肾癌相关新基因GYLZ－RCC18与肾癌细胞死亡（包括坏死及凋亡）之间的关系,并探讨肾癌基因疗法的新途径。方法：用脂质体包裹的新基因GYLZ－RCC18第一编码区起始处的20个碱基的反义和正义寡核苷酸导入肾癌细胞系GRC－1,应用流式细胞技术和伊红排斥实验连续检测GYLZ－RCC18反义寡核苷酸对肾癌细胞凋亡、坏死的影响。结果：导入GYLZ－RCC18反义寡核苷酸后,可大量杀伤GRC－1细胞并明显促进GRC－1细胞坏死,于第4天达到杀伤高峰约60％;同时可连续8d诱导凋亡峰,最高于第2天达约约22．5％,两种作用 曲线形状和峰值不完全一致。结论GYLZ－RCC18是肾癌相关的重要的新的癌基因,GYLZ－RCC18的表达可通过两种不同的机制即抗癌细胞坏死机制和抗凋亡机制发挥对肾癌细胞的保护作用,GYLZ－RCC18可能对肾癌细胞生存和耐药至关重要,通过导入反义基因的方法阻断肾癌细胞中GYLZ－RCC18的表达,可有效地杀伤肾癌细胞,对此新基因的研究将有助于为肾癌的基因的基础研究和临床治疗提供新的思路和途径。     

肾癌c-erbB-2免疫原性及临床应用的可行性研究

我们采用树突状细胞激活的杀伤性T淋巴细胞对过继免疫治疗肾癌进行研究。现报告如下。材料与方法　 2 0 0 1年我院行根治性肾切除术的新鲜肾细胞癌组织标本10例 ,其中透明细胞癌 6例、嗜色细胞癌 1例、混合细胞癌 3例 ,术后冻存待检。另取 77例包含有肿瘤和正常组织的肾癌石蜡标本切片行免疫组化检测。中国医学科学院肿瘤研究所免疫室建立的 7株人肾癌细胞系 (RCC MZHQ、RCC SKH、RCC LSL、RCC CCY、RCC WCS、RCC FTL、RCC SuL)。人肾癌细胞系RCC Krause及RCC Rupp Ⅱ为康奈尔大学惠赠 ;人乳腺癌细胞系SK BR 3作为阳…     

肾癌腹腔镜肾部分切除术的研究进展

肾细胞癌(renal cell carcinoma,RCC)是泌尿系统常见的恶性肿瘤,约占肾脏肿瘤的85%。手术治疗(包括肾部分切除术或根治性肾切除术等)是目前治疗肾癌的主要手段。RCC保留肾单位手术(nephron-sparing surgery,NSS),即在完全切除肿瘤同时有效地留     

Role of targeted therapy in combination with surgery in renal cell carcinoma

Surgical complete resection is the only curative treatment of renal cell carcinoma including patients with locally advanced disease and those with limited metastatic disease. Patients at high risk of recurrence after complete resection might theoretically benefit from adjuvant and neoadjuvant systemic treatment strategies to prolong disease‐free survival and ultimately overall survival. Another rationale for using targeted therapy includes downsizing/downstaging of surgically complex locally advanced renal cell carcinoma to facilitate complete resection or primary tumors to allow for nephron‐sparing strategies. Unfortunately, a considerable percentage of patients are diagnosed with metastatic disease at first presentation. Although large population‐based studies consistently show a survival benefit after cytoreductive nephrectomy in the targeted therapy era, confounding factors preclude definite conclusions for this heterogeneous patient group until ongoing phase III trials are published. Presurgical targeted therapy has been proposed to identify patients with clinical benefit and potentially long‐term survival after cytoreductive nephrectomy. Recently, the use of targeted therapy before or after local treatment of metastases has been reported in small retrospective series. The present review revisits the current evidence base of targeted therapy in combination with surgery for the various disease stages in renal cell carcinoma.     

Sequential therapy with targeted agents in metastatic renal cell carcinoma: beyond second-line and overcoming drug resistance

Renal cell carcinoma comprises 2–3 % of all adult malignancies and its incidence is increasing. Overall survival of patients with advanced disease has increased over the last decade due to the development of many effective targeted agents. Unfortunately, most patients inevitably develop resistance to these agents. While our understanding of the underlying resistance mechanisms has improved, there remain multiple challenges in order to overcome resistance to targeted agents. Sequential and combination therapy with a variety of novel drugs has been evaluated to maintain ongoing clinical benefit and potentially overcome drug resistance. Retrospective data suggest that further anti-angiogenic therapy may be beneficial in advanced renal cell carcinoma after prior progression on two targeted agents with a similar or different mechanism of action. However, further randomised data are needed to better define the role of these agents beyond second-line therapy in the treatment of renal cell carcinoma.     

Treatment strategies for advanced renal cell carcinoma: A new paradigm for surgical treatment

The induction of targeted drugs for the treatment of metastatic renal cell carcinoma has changed the treatment strategy for systemic therapy. Surgical treatment for metastatic renal cell carcinoma should also be reconsidered in the light of the effect of targeted drugs. The clinical benefit of cytoreductive nephrectomy for cases of metastatic renal cell carcinoma was proved in randomized trials in the cytokine era. However, at present, there has not been level 1 evidence for this in the targeted therapy era. Patients with better performance status and without poor risk factors tend to benefit from cytoreductive nephrectomy. Two ongoing large‐scale randomized studies might shed light on this issue. One of the remarkable differences in the efficacy between cytokines and targeted drugs, particularly tyrosine kinase inhibitors, is the reduction in the size of the primary tumors by tyrosine kinase inhibitors, including sunitinib and axitinib. Initial experiences with targeted therapy suggest that the neoadjuvant setting of tyrosine kinase inhibitors could be a viable option when the primary tumor shows local invasion and/or is unresectable. The present study does not support the routine neoadjuvant use of sunitinib because of the possibility of disease progression during the neoadjuvant therapy, and modest response and benefit. Axitinib, in contrast, shows larger reduction in the size of the primary tumor and might be used in the near future. Another issue is the combination of targeted therapy with metastasectomy. There is a lack of evidence for improved prognosis resulting from the neoadjuvant setting of tyrosine kinase inhibitors followed by metastasectomy. Further studies are warranted to investigate this.     

肾癌的分子靶向治疗

随着对肾癌发病机制包括细胞学、分子生物学研究的不断深入,肾癌发生中细胞信号转导通路中的一些关键分子成为治疗的靶点。以VEGF、VEGFR等为靶点的肾癌靶向治疗药物,如贝伐单抗、苏尼替尼、索拉非尼等在临床试验中已显示出很好的疗效。现就肾癌的分子靶向治疗的分子机理、临床试验研究、评价标准变化及应用前景作一简介。     

Therapy management of cardiovascular adverse events in the context of targeted therapy for metastatic renal cell carcinoma

Targeted agents have significantly improved outcomes in patients with metastatic renal cell carcinoma, and are changing long‐term expectations in these patients. Experience with these agents highlights a distinct safety and tolerability profile, differing from that observed with conventional chemotherapy and radiotherapy. Cardiovascular adverse events have been observed when treating with targeted agents. This is of particular importance for patients with metastatic renal cell carcinoma who are elderly and present with significant comorbidities. A multidisciplinary approach and close collaboration between oncologists and cardiologists is essential for optimal management of cardiovascular adverse events. Strategies for the management of these adverse events include assessment of cardiovascular status at baseline and at regular intervals, patient education, and the use of supportive medication. Effective therapy management allows patients with cardiovascular adverse events to receive and continue targeted therapy with careful monitoring. Implementation of therapy management measures contributes towards maximizing treatment outcomes with targeted agents in patients with metastatic renal cell carcinoma.     

皮肤鳞状细胞癌的研究进展

皮肤鳞状细胞癌是黑素瘤之外导致皮肤肿瘤患者死亡的首要病因。皮肤鳞状细胞癌的发病机制至今尚不明确,限制了相关分子靶向治疗的发展。目前,临床上对该病的治疗仍以手术治疗为主,辅以放射治疗等其他手段。本文结合文献对其相关研究进展进行综述。     

Recent advances in the treatment of metastatic renal cell carcinoma

In the past 5 years, the treatment of patients with metastatic renal cell carcinoma has changed dramatically from being largely cytokine‐based with the emergence of targeted therapy. Following the elucidation of various molecular pathways in renal cell carcinoma, targeted agents (particularly vascular endothelial growth factor‐targeting antiangiogenic agents) now form the backbone of most therapeutic strategies for patients with metastatic renal cell carcinoma and the outcome of treatment has improved. However, many tumors eventually develop resistance to targeted therapy due to secondary mutation of the target protein or compensatory changes within the target pathway that bypass the site of inhibition. On the other hand, there are new forms of immunotherapy that hold the promise of improving the outcome for patients with metastatic renal cell carcinoma. In this article, we describe some of these new therapies, including the anti‐vascular endothelial growth factor monoclonal antibody bevacizumab, several receptor tyrosine kinase inhibitors (sorafenib, sunitinib, pazopanib, axitinib, and tivozanib), the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and new immunotherapy modalities, such as anti‐cytotoxic T‐lymphocyte‐associated antigen 4 antibody and anti‐programmed cell death 1/programmed cell death‐ligand 1 antibody. We also discuss their role in the current management of patients with metastatic renal cell carcinoma.     

Role of metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy

Numerous biological pathways are affected in renal cell carcinoma and the introduction of targeted agents has improved the survival of patients with advanced and metastatic disease. Durable and long-lasting cure is rarely achieved, and in select cases, the excision of metastatic deposits has shown to increase survival. Clinical trials of targeted agents are being explored as neoadjuvant and adjuvant therapies with the role of metastasectomy evolving in the treatment paradigm. This review examines published reports of metastasectomy and its developing role in the era of targeted therapy. A Medline search was conducted using keywords “metastasectomy,” “renal cell carcinoma,” and “targeted therapy,” and selected articles are discussed by examining prognostic stratification and metastasectomy in major anatomic regions. Most published reports span earlier periods of immunotherapy and chemotherapy, and henceforth, discussions are in historical context in this review. Although there is lack of Level 1 evidence, reports have suggested the prognostic value and survival benefit for metastasectomy in lesions that are amenable to complete resection after longer disease-free intervals in carefully selected patients with adequate performance status. Therefore, the role of metastasectomy must be further elucidated in the era of targeted therapy.     

Prognostic factors and risk classifications for patients with metastatic renal cell carcinoma

The introduction of molecular‐targeted therapy has made dramatical changes to treatment for metastatic renal cell carcinoma. Currently, there are four vascular endothelial growth factor receptor‐tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors in Japan. For the appropriate clinical use of these molecular‐targeted drugs, the identification of prognostic and/or predictive factors in patients who received these drugs is required. Although molecular biological and genetic factors that determine the prognosis of patients with metastatic renal cell carcinoma have been reported, most of these factors are problematic in that the number of patients analyzed was small. In contrast, clinicopathological prognostic factors, including the practice of cytoreductive nephrectomy, pathological findings, metastatic sites and metastasectomy, and abnormal inflammatory response, have been identified by analyzing a relatively large number of patients. Several prognostic classification models that were developed by combining these clinicopathological factors are widely used in not only clinical trials, but also routine clinical practice. However, the quality of these prognostic models is considered to be insufficient regarding prognostic prediction of metastatic renal cell carcinoma patients and, thus, requires further improvements. Recently, basic and clinical studies have been extensively carried out for the identification of promising informative markers and for understanding molecular mechanisms of resistance to molecular‐targeted drugs in metastatic renal cell carcinoma patients. The present review considers ongoing translational research efforts on clinicopathological, molecular biological, and genetic prognostic and/or predictive factors for metastatic renal cell carcinoma patients in the era of molecular‐targeted therapy, and discusses the clinical implications of these findings.     

Neoadjuvant treatment of renal cell carcinoma

Renal cell carcinoma is a potentially devastating cancer, and when metastatic, remains incurable with currently available systemic therapy. Surgical nephrectomy remains the only proven modality which can offer curative options for patients with resectable disease. Further, cytoreductive nephrectomy continues to play a role in the metastatic disease setting. The use of targeted therapy as an adjunct to surgical resection is beginning to be explored in both of these clinical scenarios. Immediate questions regarding preoperative treatment with VEGF pathway targeted therapy include issues surrounding the safety of these agents in use in the perioperative time period, the expectations for response in the primary tumor, the optimal duration of therapy, and the clinical settings in which this therapy may be most beneficial. This review will discuss the current experience with neoadjuvant or preoperative therapy in locally advanced or metastatic renal cell carcinoma and will overview the challenges and opportunities which lie ahead for this form of multimodality therapy.