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Tumor physiology and drug resistance
1Department of Medical Oncology, Princess Margaret Hospital and University of Toronto, ON, Canada. ian.tannock@uhn.on.ca
Cancer Metastasis Reviews
|February 8, 2002
Summary
Clinical drug resistance in solid tumors is not solely due to genetic mutations. Tumor physiology, microenvironment, and drug penetration significantly impact treatment outcomes, suggesting new therapeutic strategies.
Area of Science:
- Oncology
- Pharmacology
- Tumor Biology
Background:
- Clinical drug resistance is often attributed to pre-existing or selected drug-resistant tumor cells.
- However, this perspective may not fully account for the complexity of resistance in solid tumors.
Purpose of the Study:
- To review and highlight non-genetic factors contributing to clinical drug resistance in solid tumors.
- To emphasize the role of tumor physiology, microenvironment, and three-dimensional structure in drug efficacy.
Main Methods:
- This is a review article, synthesizing existing research on clinical drug resistance mechanisms.
- Emphasis is placed on factors beyond single-cell genetic determinants.
Main Results:
- Genetically determined cellular resistance is only one facet of clinical resistance.
- Limited drug penetration from tumor vasculature and tumor cell repopulation between chemotherapy cycles are significant contributors to resistance.
- These physiological factors can be modulated to improve therapeutic outcomes.
Conclusions:
- Clinical drug resistance in solid tumors is multifactorial, involving more than just genetic resistance at the cellular level.
- Understanding and targeting tumor physiology and microenvironment are crucial for overcoming resistance.
- Relying solely on single-cell resistance mechanisms, like reversing multidrug resistance, may lead to clinical trial failures.