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肾癌的基础研究。

Basic research in kidney cancer.

机构信息

Department of Urology, University Medical Centre Nijmegen, Nijmegen, The Netherlands.

出版信息

Eur Urol. 2011 Oct;60(4):622-33. doi: 10.1016/j.eururo.2011.06.048. Epub 2011 Jul 5.

Abstract

CONTEXT

Advances in basic research will enhance prognosis, diagnosis, and treatment of renal cancer patients.

OBJECTIVE

To discuss advances in our understanding of the molecular basis of renal cancer, targeted therapies, renal cancer and immunity, and genetic factors and renal cell carcinoma (RCC).

EVIDENCE ACQUISITION

Data on recently published (2005-2011) basic science papers were reviewed.

EVIDENCE SYNTHESIS

Advances in basic research have shown that renal cancers can be subdivided based on specific genetic profiles. Now that this molecular basis has been established, it is becoming clear that additional events play a major role in the development of renal cancer. For example, aberrant chromatin remodelling appears to be a main driving force behind tumour progression in clear cell RCC. A large number of potential biomarkers have emerged using various high-throughput platforms, but adequate biomarkers for RCC are still lacking. To bring the potential biomarkers and biomarker profiles to the clinical arena is a major challenge for the field. The introduction of tyrosine kinase inhibitors (TKIs) for therapy has shifted the interest away from immunologic approaches. Nevertheless, a wealth of evidence supports immunotherapy for RCC. Interestingly, studies are now appearing that suggest a combination of TKI and immunotherapy may be beneficial. Thus far, little attention has been paid to patient-specific differences. With high-throughput methods becoming cheaper and with the advances in sequencing possibilities, this situation is expected to change rapidly.

CONCLUSIONS

Great strides have been made in the understanding of molecular mechanisms of RCC. This has led this field to the enviable position of having a range of molecularly targeted therapies. Large sequencing efforts are now revealing more and more genes responsible for tumour development and progression, offering new targets for therapy. It is foreseen that through integration of high-throughput platforms, personalised cancer treatment for RCC patients will become possible.

摘要

背景

基础研究的进展将提高肾癌患者的预后、诊断和治疗水平。

目的

讨论我们对肾癌分子基础、靶向治疗、肾癌与免疫、遗传因素与肾细胞癌理解的进展。

资料来源

回顾了最近发表的(2005-2011 年)基础科学论文的数据。

综合分析

基础研究的进展表明,肾癌可以根据特定的遗传特征进行细分。既然已经确定了这个分子基础,那么很明显,其他因素在肾癌的发生发展中起着重要作用。例如,异常染色质重塑似乎是透明细胞肾细胞癌肿瘤进展的主要驱动力。大量的潜在生物标志物已经通过各种高通量平台出现,但仍然缺乏足够的肾癌生物标志物。将潜在的生物标志物和生物标志物图谱应用于临床领域是该领域的一个主要挑战。酪氨酸激酶抑制剂(TKI)治疗的引入使人们对免疫治疗的兴趣转移。然而,大量证据支持免疫治疗肾癌。有趣的是,现在出现的研究表明 TKI 和免疫治疗的联合可能是有益的。到目前为止,很少关注患者的个体差异。随着高通量方法变得更加便宜,测序可能性的进步,这种情况预计将迅速改变。

结论

在理解肾细胞癌的分子机制方面取得了重大进展。这使得该领域具有一系列针对分子靶点的治疗方法。大规模的测序工作现在揭示了越来越多与肿瘤发生和发展有关的基因,为治疗提供了新的靶点。可以预见,通过整合高通量平台,将有可能为肾癌患者提供个性化的癌症治疗。

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