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精准医学时代的放射性药物治疗。

Radiopharmaceutical therapy in the era of precision medicine.

作者信息

Sgouros George, Goldenberg David M

机构信息

Division of Nuclear Medicine, Dept. of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, NJ, United States.

出版信息

Eur J Cancer. 2014 Sep;50(13):2360-3. doi: 10.1016/j.ejca.2014.04.025. Epub 2014 Jun 19.

Abstract

Precision medicine is the selection of a treatment modality that is specifically tailored to the genetic and phenotypic characteristics of a particular patient's disease. In cancer, the objective is to treat with agents that inhibit cell signalling pathways that drive uncontrolled proliferation and dissemination of the disease. To overcome the eventual resistance to pathway inhibition therapy, this treatment modality has been combined with chemotherapy. We propose that pathway inhibition therapy is more rationally combined with radiopharmaceutical therapy (RPT), a cytotoxic treatment that is also targeted. RPT exploits pharmaceuticals that either bind specifically to tumours or accumulate by a broad array of physiological mechanisms indigenous to the neoplastic cells to deliver radiation specifically to these cells. Consistent with pathway inhibition therapy and in contrast to chemotherapy, RPT is well tolerated. However, the potential of RPT has not been fully exploited; for the most part, treatment has been implemented without using the ability to customise RPT by imaging and deriving individual patient tumour and normal organ radiation absorbed doses. These are more closely related to biological response and their determination should enable RPT treatment administration to maximum therapeutic benefit by treating to normal organ tolerance or demonstrating futility via tumour dosimetry. This is the essence of precision medicine.

摘要

精准医学是选择一种专门针对特定患者疾病的基因和表型特征量身定制的治疗方式。在癌症治疗中,目标是使用能够抑制驱动疾病不受控制地增殖和扩散的细胞信号通路的药物进行治疗。为了克服最终对通路抑制疗法产生的耐药性,这种治疗方式已与化疗相结合。我们提出通路抑制疗法与放射性药物疗法(RPT)更合理地联合使用,RPT是一种同样具有靶向性的细胞毒性治疗方法。RPT利用的药物要么特异性结合肿瘤,要么通过肿瘤细胞固有的多种生理机制聚集,从而将辐射特异性地传递给这些细胞。与通路抑制疗法一致且与化疗不同,RPT耐受性良好。然而,RPT的潜力尚未得到充分开发;在大多数情况下,治疗实施时并未利用通过成像定制RPT以及推导个体患者肿瘤和正常器官辐射吸收剂量的能力。这些与生物学反应更为密切相关,其测定应能通过根据正常器官耐受性进行治疗或通过肿瘤剂量测定证明无效,使RPT治疗实现最大治疗效益。这就是精准医学的本质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/4119492/cd67ee517358/nihms601095f1.jpg

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