Lysosome-directed targeted protein degradation technologies for overcoming cancer drug resistance: mechanisms, design principles, and therapeutic opportunities

Drug Delivery 2026 Open access

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Authors: Huixin Mao, Ying Zhang, Mingqi Liu, Yao Yao, Yujie Peng, Xuwei Zhou, Hao Huang, Weidong Fei, Caihong Zheng, Yiqing Ye
DOI: 10.1080/10717544.2026.2679844
Cited by: 1
References: 68

Abstract

pharmacological behaviors, with particular emphasis on stability, tumor selectivity, and degradation efficiency. Importantly, this article comprehensively highlights recent advances in the application of LYTACs for overcoming therapeutic resistance, including resistance to chemotherapy, targeted therapy, and immunotherapy. Finally, current translational bottlenecks, such as delivery efficiency, receptor heterogeneity, and pharmacokinetic limitations, are critically analyzed. Collectively, while still in its early stages of development, LYTAC-based lysosomal degradation represents a promising, paradigm-shifting strategy for targeting previously intractable mechanisms of cancer resistance.

Fields of Study & Subjects

Protein Degradation and Inhibitors Click Chemistry and Applications Peptidase Inhibition and Analysis

Publication details

Journal / source
Drug Delivery
Publisher
Informa UK Limited
Volume
33
Issue
1
Pages
2679844–2679844
Publication date
27 May 2026
Language
EN