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预测性生物标志物的重要性及其与实体瘤免疫治疗反应的相关性——对临床实践的影响

The Importance of Predictive Biomarkers and Their Correlation with the Response to Immunotherapy in Solid Tumors-Impact on Clinical Practice.

作者信息

Mihaila Raluca Ioana, Gheorghe Adelina Silvana, Zob Daniela Luminita, Stanculeanu Dana Lucia

机构信息

Department of Oncology, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.

Department of Medical Oncology I, "Prof. Dr. Alexandru Trestioreanu", Institute of Oncology, 022328 Bucharest, Romania.

出版信息

Biomedicines. 2024 Sep 22;12(9):2146. doi: 10.3390/biomedicines12092146.

Abstract

: Immunotherapy has changed the therapeutic approach for various solid tumors, especially lung tumors, malignant melanoma, renal and urogenital carcinomas, demonstrating significant antitumor activity, with tolerable safety profiles and durable responses. However, not all patients benefit from immunotherapy, underscoring the need for predictive biomarkers that can identify those most likely to respond to treatment. The integration of predictive biomarkers into clinical practice for immune checkpoint inhibitors (ICI) holds great promise for personalized cancer treatment. Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), microsatellite instability (MSI), gene expression profiles and circulating tumor DNA (ctDNA) have shown potential in predicting ICI responses across various cancers. : Challenges such as standardization, validation, regulatory approval, and cost-effectiveness must be addressed to realize their full potential. Predictive biomarkers are crucial for optimizing the clinical use of ICIs in cancer therapy. : While significant progress has been made, further research and collaboration among clinicians, researchers, and regulatory institutes are essential to overcome the challenges of clinical implementation. However, little is known about the relationship between local and systemic immune responses and the correlation with response to oncological therapies and patient survival.

摘要

免疫疗法已经改变了各种实体瘤的治疗方法,尤其是肺癌、恶性黑色素瘤、肾癌和泌尿生殖系统癌,显示出显著的抗肿瘤活性,且安全性可耐受、反应持久。然而,并非所有患者都能从免疫疗法中获益,这凸显了对预测性生物标志物的需求,这些标志物能够识别出最有可能对治疗产生反应的患者。将预测性生物标志物整合到免疫检查点抑制剂(ICI)的临床实践中,对个性化癌症治疗具有巨大的前景。程序性死亡配体1(PD-L1)表达、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、基因表达谱和循环肿瘤DNA(ctDNA)在预测各种癌症的ICI反应方面已显示出潜力。必须解决标准化、验证、监管批准和成本效益等挑战,以充分发挥其潜力。预测性生物标志物对于优化ICI在癌症治疗中的临床应用至关重要。虽然已经取得了重大进展,但临床医生、研究人员和监管机构之间的进一步研究与合作对于克服临床实施中的挑战至关重要。然而,关于局部和全身免疫反应之间的关系以及与肿瘤治疗反应和患者生存的相关性,我们知之甚少。

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