揭示胰腺癌免疫治疗的关键靶点。

Uncovering key targets of success for immunotherapy in pancreatic cancer.

机构信息

Medical Oncology Unit, Sapienza University of Rome, Rome Italy.

Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy.

出版信息

Expert Opin Ther Targets. 2021 Nov;25(11):987-1005. doi: 10.1080/14728222.2021.2010044. Epub 2021 Dec 13.

Abstract

INTRODUCTION

Despite available treatment options, pancreatic ductal adenocarcinoma (PDAC) is frequently lethal. Recent immunotherapy strategies have failed to yield any notable impact. Therefore, research is focussed on unearthing new drug targets and therapeutic strategies to tackle this malignancy and attain more positive outcomes for patients.

AREAS COVERED

In this perspective article, we evaluate the main resistance mechanisms to immune checkpoint inhibitors (ICIs) and the approaches to circumvent them. We also offer an assessment of concluded and ongoing trials of PDAC immunotherapy. Literature research was performed on Pubmed accessible through keywords such as: 'pancreatic ductal adenocarcinoma,' 'immunotherapy,' 'immunotherapy resistance,' 'immune escape,' 'biomarkers.' Papers published between 2000 and 2021 were selected.

EXPERT OPINION

The tumor microenvironment is a critical variable of treatment resistance because of its role as a physical barrier and inhibitory immune signaling. Promising therapeutic strategies appear to be a combination of immunotherapeutics with other targeted treatments. Going forward, predictive biomarkers are required to improve patient selection. Biomarker-driven trials could enhance approaches for assessing the role of immunotherapy in PDAC.

摘要

简介

尽管有可用的治疗方法,但胰腺导管腺癌 (PDAC) 仍然常常致命。最近的免疫疗法策略未能产生任何显著影响。因此,研究集中在挖掘新的药物靶点和治疗策略上,以解决这种恶性肿瘤,并为患者带来更积极的结果。

涵盖领域

在这篇观点文章中,我们评估了免疫检查点抑制剂 (ICI) 的主要耐药机制及其规避方法。我们还对已完成和正在进行的 PDAC 免疫治疗试验进行了评估。通过关键词如“胰腺导管腺癌”、“免疫疗法”、“免疫疗法耐药性”、“免疫逃逸”、“生物标志物”在 Pubmed 上进行了文献研究。选择了 2000 年至 2021 年期间发表的论文。

专家意见

肿瘤微环境是治疗耐药性的一个关键变量,因为它是物理屏障和抑制性免疫信号的作用。有前途的治疗策略似乎是将免疫疗法与其他靶向治疗相结合。未来,需要预测性生物标志物来改善患者选择。基于生物标志物的试验可以增强评估免疫疗法在 PDAC 中作用的方法。

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