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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

Mechanisms of Anti-PD Therapy Resistance in Digestive System Neoplasms

In Press, (this is not the final "Version of Record"). Available online 04 January, 2024
Author(s): Yuxia Wu, Xiangyan Jiang, Zeyuan Yu*, Zongrui Xing, Yong Ma and Huiguo Qing
Published on: 04 January, 2024

DOI: 10.2174/0115748928269276231120103256

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Abstract

Digestive system neoplasms are highly heterogeneous and exhibit complex resistance mechanisms that render anti-programmed cell death protein (PD) therapies poorly effective. The tumor microenvironment (TME) plays a pivotal role in tumor development, apart from supplying energy for tumor proliferation and impeding the body's anti-tumor immune response, the TME actively facilitates tumor progression and immune escape via diverse pathways, which include the modulation of heritable gene expression alterations and the intricate interplay with the gut microbiota. In this review, we aim to elucidate the mechanisms underlying drug resistance in digestive tumors, focusing on immune-mediated resistance, microbial crosstalk, metabolism, and epigenetics. We will highlight the unique characteristics of each digestive tumor and emphasize the significance of the tumor immune microenvironment (TIME). Furthermore, we will discuss the current therapeutic strategies that hold promise for combination with cancer immune normalization therapies. This review aims to provide a thorough understanding of the resistance mechanisms in digestive tumors and offer insights into potential therapeutic interventions.

Keywords: Immunotherapy resistance, normalization cancer immunotherapy, PD-1/B7-H1, anti-PD-1/PD-L1 therapy, digestive system neoplasms.


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