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Updated: May 22, 2025
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Overcoming cancer therapy resistance: From drug innovation to therapeutics
Jin-Rui Wei1, Meng-Yi Lu2, Tian-Hua Wei3
1Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210029, China; The First Clinical College of Nanjing University of Chinese Medicine, Nanjing 210023, China.
Abstract:
One of the major limitations of cancer therapy is the emergence of drug resistance. This review amis to provide a focused analysis of the multifactorial mechanisms underlying therapy resistance,with an emphasis on actionable insights for developing novel therapeutic strategies. It concisely outlines key factors contributing to therapy resistance, including drug delivery barriers, cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), cancer heterogeneity, tumor microenvironment (TME), genetic mutations, and alterlations in gene expression. Additionally, we explore how tumors evade targeted therapies through pathway-specific mechanisms that restore disrupted signaling pathways. The review critically evaluates innovative strategies designed to sensitize resistant tumor cells, such as targeted protein dedgradation, antibody-drug conjugates, structure-based drug design, allosteric drugs, multitarget drugs, nanomedicine and others We also highlight the importance of understanding the pharmacological actions of these agents and their integration into treatment regimens. By synthesizing current knowledge and identifying gaps in our understanding, this review aims to guide future research and improve patient outcomes in cancer therapy.
Insights
Cancer drug resistance is a major challenge. This review explores resistance mechanisms and novel strategies like targeted protein degradation and nanomedicine to overcome it, aiming to improve cancer therapy outcomes.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Drug resistance is a significant limitation in cancer therapy, leading to treatment failure.
- Multifactorial mechanisms contribute to therapy resistance, necessitating a comprehensive understanding.
Purpose of the Study:
- To analyze the complex mechanisms of cancer therapy resistance.
- To provide actionable insights for developing novel therapeutic strategies against resistant tumors.
Main Methods:
- Literature review focusing on key factors contributing to resistance.
- Evaluation of innovative strategies to sensitize resistant cancer cells.
- Synthesis of current knowledge and identification of research gaps.
Main Results:
- Identified key resistance factors: drug delivery barriers, cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), tumor heterogeneity, tumor microenvironment (TME), genetic mutations, and altered gene expression.
- Explored evasion mechanisms of targeted therapies via pathway restoration.
- Evaluated novel therapeutic strategies including targeted protein degradation, antibody-drug conjugates, nanomedicine, and others.
Conclusions:
- Understanding resistance mechanisms is crucial for improving cancer therapy.
- Innovative strategies show promise in overcoming drug resistance and enhancing patient outcomes.
- Further research is needed to integrate these agents effectively into treatment regimens.
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