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开发用于治疗胰腺腺癌的生物制剂的范式转变。

Shifting paradigm of developing biologics for the treatment of pancreatic adenocarcinoma.

作者信息

Zeng Ying, Rucki Agnieszka A, Che Xu, Zheng Lei

机构信息

Department of Medical Oncology, Geisinger Medical Center, Danville, PA 17822, USA.

Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

出版信息

J Gastrointest Oncol. 2017 Jun;8(3):441-448. doi: 10.21037/jgo.2016.10.02.

Abstract

Pancreatic adenocarcinoma is still widely considered as a deadly disease even though there are substantial therapeutic developments in the past decade. Using combinational chemotherapy regimens, represented by gemcitabine plus nab-paclitaxel and FOLFIRINOX, was able to improve overall survival in patients with advanced disease to a limited extent. It has been a challenge to develop targeted therapies that are focused on the neoplasm cells of pancreatic adenocarcinoma. Recently, targeting the stroma and immune compartments of pancreatic adenocarcinoma has shown promising results. The paradigm of biologics drug development therefore has been shifted by extending to these exciting areas. Although some of the preclinical and clinical researches in targeting the tumor microenvironment of pancreatic adenocarcinoma have shown promising results, others have resulted in controversial findings. Both comprehensive and in-depth researches on the basic science of the tumor microenvironment of pancreatic adenocarcinoma are thus warranted for the development of effective biologics that target the tumor microenvironment. Moreover, an ideal treatment for pancreatic adenocarcinoma shall be a combination of targeting both neoplastic cells and the tumor microenvironment.

摘要

尽管在过去十年中治疗方法有了重大进展,但胰腺腺癌仍被广泛认为是一种致命疾病。使用以吉西他滨加纳米白蛋白结合型紫杉醇和FOLFIRINOX为代表的联合化疗方案,能够在一定程度上提高晚期患者的总生存期。开发针对胰腺腺癌细胞的靶向治疗一直是一项挑战。最近,针对胰腺腺癌的基质和免疫区室进行靶向治疗已显示出有希望的结果。因此,生物制剂药物开发的模式已扩展到这些令人兴奋的领域,从而发生了转变。尽管一些针对胰腺腺癌肿瘤微环境的临床前和临床研究已显示出有希望的结果,但其他研究却得出了有争议的结果。因此,为了开发针对肿瘤微环境的有效生物制剂,有必要对胰腺腺癌肿瘤微环境的基础科学进行全面深入的研究。此外,理想的胰腺腺癌治疗方法应该是同时靶向肿瘤细胞和肿瘤微环境。

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