Do Chris T P, Prochnau Jack Y, Dominguez Angel, Wang Pei, Rao Manjeet K
Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Biomedicines. 2024 Sep 2;12(9):1979. doi: 10.3390/biomedicines12091979.
This review explores the challenges and emerging trends in pancreatic cancer therapy. In particular, we focus on the tumor microenvironment and the potential of immunotherapy for pancreatic cancer. Pancreatic ductal adenocarcinoma, characterized by its dense stromal architecture, presents unique challenges for effective treatment. Recent advancements have emphasized the role of the tumor microenvironment in therapeutic resistance and disease progression. We discuss novel strategies targeting the desmoplastic barrier and immunosuppressive cells to enhance immune cell infiltration and activation. Recent clinical trials, particularly those involving novel immunotherapeutic agents and tumor vaccines, are examined to understand their efficacy and limitations. Our analysis reveals that combining immunotherapy with chemotherapy, radiation therapy, or drugs targeting epigenetic processes shows promise, improving overall survival rates and response to treatment. For instance, trials utilizing checkpoint inhibitors in combination with standard chemotherapies have extended disease-free survival by up to 6 months compared to chemotherapy alone. Importantly, vaccines targeting specific tumor neoantigens have shown the potential to increase patient survival. However, these approaches also face significant challenges, including overcoming the immunosuppressive tumor microenvironment and enhancing the delivery and efficacy of therapeutic agents. By providing an overview of both the promising results and the obstacles encountered, this review aims to highlight ongoing efforts to refine immunotherapy approaches for better patient outcomes.
本综述探讨了胰腺癌治疗中的挑战和新趋势。特别是,我们关注肿瘤微环境以及胰腺癌免疫治疗的潜力。以密集的基质结构为特征的胰腺导管腺癌,在有效治疗方面面临独特挑战。最近的进展强调了肿瘤微环境在治疗耐药性和疾病进展中的作用。我们讨论了针对促结缔组织增生性屏障和免疫抑制细胞的新策略,以增强免疫细胞浸润和激活。对最近的临床试验,特别是那些涉及新型免疫治疗药物和肿瘤疫苗的试验进行了研究,以了解它们的疗效和局限性。我们的分析表明,将免疫治疗与化疗、放射治疗或靶向表观遗传过程的药物联合使用显示出前景,可提高总体生存率和对治疗的反应。例如,与单纯化疗相比,使用检查点抑制剂与标准化疗联合的试验已将无病生存期延长了多达6个月。重要的是,靶向特定肿瘤新抗原的疫苗已显示出提高患者生存率的潜力。然而,这些方法也面临重大挑战,包括克服免疫抑制性肿瘤微环境以及提高治疗药物的递送和疗效。通过概述既有前景的结果和遇到的障碍,本综述旨在突出为改善患者预后而不断努力优化免疫治疗方法的情况。