Functional genomic identification of predictive biomarkers of everolimus sensitivity and of new molecular targets in ren

依维莫司是一种治疗肾癌的有效新药，但并非所有患者都对依维莫司有反应，即使有反应的患者在治疗6-9个月后也会产生耐药性。我们将使用一种名为“功能基因组学”的技术，在实验室中生长的肾癌细胞中单独灭活21000个人类基因中的每一个，以识别可能导致依维莫司耐药的基因。将进一步研究抗性基因，以了解抗性如何发展以及如何预防或治疗。我们还将分析来自接受依维莫司治疗的患者的肾癌样本，以确定所鉴定的耐药基因是否在耐药癌症中普遍改变。这将导致开发一种测试，可以确定肾癌患者是否可能在治疗开始前对依维莫司产生反应。这样的测试将使耐药疾病患者免受治疗的副作用，并提高他们的生活质量。依维莫司由于成本高而未被批准用于NHS。一项允许将该药物靶向治疗敏感疾病患者的测试将降低总体成本，并希望将其提供给NHS患者。

Everolimus is an effective new drug for the treatment of kidney cancer, however not all patients respond to everolimus and even those who respond develop resistance after 6-9 months of treatment. We will use a technique called ‘functional genomics‘ to de-activate each of the 21.000 human genes individually in kidney cancer cells grown in the laboratory, to identify genes that can lead to everolimus resistance. Resistance genes will be further studies to understand how resistance develops and how it can be prevented or treated. We will also analyse kidney cancer samples from patients treated with everolimus to determine whether the identified resistance genes are commonly altered in resistant cancers. This should lead to the development of a test that can determine whether a patient with kidney cancer is likely to respond to everolimus before treatment is actually started. Such a test would spare patients with resistant disease the side effects of the treatment and improve their quality of life. Everolimus is not approved for the use in the NHS because of the high costs. A test that allows targeting the drug to patients with sensitive disease would reduce overall costs and hopefully make it available to NHS patients.