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癌症患者的个体化治疗:是临床实践中的现实,还是肿瘤学界的昂贵梦想或共同愿景?

Personalized treatments of cancer patients: a reality in daily practice, a costly dream or a shared vision of the future from the oncology community?

机构信息

Department of Medicine, Gustave Roussy, Villejuif, France; Inserm Unit U981, Gustave Roussy, Villejuif, France.

Department of Medicine, Gustave Roussy, Villejuif, France.

出版信息

Cancer Treat Rev. 2014 Dec;40(10):1192-8. doi: 10.1016/j.ctrv.2014.07.002. Epub 2014 Jul 17.

Abstract

Therapies targeting activated oncogenes have been associated with several successes in the last decades that are described in this review, together with their limits and related unsolved questions. Most of the tumours will eventually develop drug resistance potentially due to intratumor heterogeneity and selection of additional molecular events. Moreover, studies in the field of molecular characterisation of cancers have shown that most tumors include large number of rare genomic events. Developing new drugs requires the use of large-scale molecular screening programs to enrich phase I/II trials with patients presenting the genetic alterations to treat them with the appropriate drug(s). Administering one single drug will incur in non-durable results, so the future is to cleverly combine drugs. Development of personalized immunotherapeutics and/or anti-angiogenic agents could change the natural history of several cancers. Finally, other systems including DNA repair and metabolism have become targetable. These considerations justify the development of molecular medicine with the characterisation of each tumour to assess defects in all the systems previously mentioned to propose a unique combination of therapies to each patient. Current drug development is clearly not appropriate, and studies with drugs given in relevant combinations should be favoured by new relationships between academia and industry. New organisational and medico-economics approaches are required to minimize the financial burden of personalized medicine by considering the foreseen decrease of the costs of new technologies, and the money saved by avoiding the use of many costly, useless but nonetheless toxic treatments given after failure of standard therapy.

摘要

在过去几十年中,靶向激活癌基因的治疗方法取得了一些成功,本文对这些成功进行了描述,同时也探讨了它们的局限性和相关的未解决问题。大多数肿瘤最终会产生耐药性,这可能是由于肿瘤内异质性和其他分子事件的选择。此外,癌症分子特征研究表明,大多数肿瘤包含大量罕见的基因组事件。开发新药需要使用大规模的分子筛选计划,在 I/II 期试验中富集具有遗传改变的患者,以便用适当的药物治疗他们。单一药物治疗会导致不可持久的结果,因此未来的趋势是巧妙地联合使用药物。个性化免疫治疗和/或抗血管生成药物的发展可能会改变几种癌症的自然病程。最后,其他系统,包括 DNA 修复和代谢,也已成为可靶向的目标。这些考虑因素证明了分子医学的发展是合理的,需要对每个肿瘤进行特征分析,以评估前面提到的所有系统中的缺陷,为每个患者提出独特的联合治疗方案。目前的药物开发显然是不合适的,应该鼓励学术界和工业界之间建立新的关系,开展相关药物联合治疗的研究。需要新的组织和医疗经济学方法,通过考虑预计的新技术成本降低,以及避免在标准治疗失败后使用许多昂贵、无用但仍有毒性的治疗方法来节省资金,从而最大限度地降低个性化医学的经济负担。

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