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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

Zhen-Duo Shi1,2,3,4, Kun Pang1,2, Zhuo-Xun Wu5

  • 1Department of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.

Signal Transduction and Targeted Therapy
|March 11, 2023
PubMed

Insights

Tumor cell plasticity drives resistance to targeted cancer therapies. Strategies targeting or reversing this plasticity offer new hope for overcoming treatment evasion and improving patient outcomes.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Therapeutics

Background:

  • Targeted therapies have improved cancer treatment, but therapy-induced resistance remains a significant challenge.
  • Tumor cells exhibit phenotypic plasticity, enabling evasion of treatments and relapse.
  • Mechanisms of plasticity include epigenetic changes, signaling pathway modulation, and tumor microenvironment alterations.

Purpose of the Study:

  • To review the mechanisms of tumor cell plasticity and its role in evading targeted therapies.
  • To discuss non-genetic drivers of drug-induced plasticity and their contribution to acquired resistance.
  • To present novel therapeutic strategies and ongoing clinical trials targeting tumor cell plasticity.

Main Methods:

  • Literature review of mechanisms driving tumor cell plasticity.
  • Analysis of non-genetic factors contributing to acquired drug resistance.
  • Discussion of emerging therapeutic approaches and clinical trial data.

Main Results:

  • Tumor cell plasticity, including epithelial-to-mesenchymal transition and cancer stem cell formation, is a key driver of targeted therapy resistance.
  • Non-genetic mechanisms are crucial in inducing and maintaining tumor cell plasticity.
  • Targeting plasticity-related mechanisms shows promise in overcoming acquired resistance.

Conclusions:

  • Tumor cell plasticity is a critical mechanism of acquired resistance to targeted cancer therapies.
  • Inhibiting or reversing tumor cell plasticity presents a promising therapeutic avenue.
  • Further research and clinical trials are essential to develop effective combination therapies targeting tumor cell plasticity.

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