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检查点抑制剂治疗的新型生物标志物。

New biomarkers for checkpoint inhibitor therapy.

机构信息

Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.

出版信息

ESMO Open. 2020 Sep;5(Suppl 1):e000597. doi: 10.1136/esmoopen-2019-000597.

Abstract

Immune checkpoint inhibitor blockade has vastly changed treatment paradigms and improved outcomes of many solid organ malignancies. The achievements of the last decade have transformed the outcomes of several tumour types, most notably metastatic melanoma. There are, however, still large numbers of patients who receive checkpoint inhibitor therapy and do not respond. In addition to potential lack of efficacy, checkpoint inhibitors also come with a unique and sometimes devastating side-effect profile. There exists a strong need for biomarkers to accurately predict response, improve treatment selection and avoid exposing patients to toxicity where there is minimal likelihood of response. There is a wide range of methodologies investigating predictive biomarkers in this space; in this review, we address the major putative biomarkers of interest. These include conventional serum tests such as lymphocyte indices and lactate dehydrogenase, and more novel research markers such as interleukin-6 and T receptor clonality. We discuss tumorous factors that may be of interest in certain tumour types, and finally gene expression profiling. Significant research continues into many of these potential predictive biomarkers in response to the emergent need to better select patients who will benefit from treatment.

摘要

免疫检查点抑制剂阻断疗法极大地改变了许多实体恶性肿瘤的治疗模式,并改善了治疗效果。过去十年的成就改变了几种肿瘤类型的治疗结果,尤其是转移性黑色素瘤。然而,仍有大量接受检查点抑制剂治疗但无应答的患者。除了潜在的疗效不足外,检查点抑制剂还具有独特且有时具有破坏性的副作用谱。因此,非常需要生物标志物来准确预测反应、改善治疗选择,并避免在应答可能性极小的情况下使患者暴露于毒性中。在这一领域有多种方法研究预测性生物标志物;在这篇综述中,我们探讨了主要的潜在生物标志物。这些标志物包括常规血清检测,如淋巴细胞指数和乳酸脱氢酶,以及更新型的研究标志物,如白细胞介素-6 和 T 受体克隆性。我们讨论了在某些肿瘤类型中可能具有研究价值的肿瘤因素,最后是基因表达谱。由于需要更好地选择受益于治疗的患者,因此,许多潜在的预测性生物标志物的研究仍在继续。

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