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Updated: Dec 6, 2025
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Emerging role of tumor cell plasticity in modifying therapeutic response
Siyuan Qin1, Jingwen Jiang1, Yi Lu2,3
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, 610041, Chengdu, People's Republic of China.
Abstract:
Resistance to cancer therapy is a major barrier to cancer management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance, the latter of which is the focus that will be discussed here. Such non-mutational processes are largely driven by tumor cell plasticity, which renders tumor cells insusceptible to the drug-targeted pathway, thereby facilitating the tumor cell survival and growth. The concept of tumor cell plasticity highlights the significance of re-activation of developmental programs that are closely correlated with epithelial-mesenchymal transition, acquisition properties of cancer stem cells, and trans-differentiation potential during drug exposure. From observations in various cancers, this concept provides an opportunity for investigating the nature of anticancer drug resistance. Over the years, our understanding of the emerging role of phenotype switching in modifying therapeutic response has considerably increased. This expanded knowledge of tumor cell plasticity contributes to developing novel therapeutic strategies or combination therapy regimens using available anticancer drugs, which are likely to improve patient outcomes in clinical practice.
Insights
Non-mutational resistance mechanisms, driven by tumor cell plasticity, allow cancer cells to survive drug treatment. Understanding this plasticity is key to developing new cancer therapies and improving patient outcomes.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Biology
Background:
- Cancer therapy resistance is a significant obstacle in cancer management.
- Traditionally, genetic mutations were considered the primary cause of resistance.
- Emerging evidence points to non-mutational mechanisms, particularly drug tolerance, as crucial.
Purpose of the Study:
- To discuss the role of non-mutational resistance mechanisms in cancer drug tolerance.
- To explore how tumor cell plasticity drives these resistance mechanisms.
- To highlight the potential of targeting tumor cell plasticity for improved cancer therapy.
Main Methods:
- Review of accumulating evidence on non-mutational resistance.
- Analysis of the concept of tumor cell plasticity and its drivers.
- Examination of phenotype switching and its impact on therapeutic response.
Main Results:
- Non-mutational processes, driven by tumor cell plasticity, enable cancer cell survival and growth despite drug exposure.
- Tumor cell plasticity involves the reactivation of developmental programs, including epithelial-mesenchymal transition and cancer stem cell properties.
- Phenotype switching plays a significant role in modifying therapeutic response across various cancers.
Conclusions:
- Tumor cell plasticity is a critical factor in anticancer drug resistance and tolerance.
- Understanding phenotype switching offers new avenues for therapeutic strategies.
- Targeting tumor cell plasticity may lead to novel combination therapies and improved patient outcomes.
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