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Multicellular resistance: a paradigm for clinical resistance?
1Laboratoire de Biochimie et de Biologie Moléculaire, Faculté de Pharmacie, IFR 51, EA 2063, Reims, France. bernard.desoize@univ-reims.fr
Critical Reviews in Oncology/Hematology
|October 18, 2000
Summary
Multicellular resistance (MCR) in tumors poses a challenge to cancer treatment. Hyaluronidase may overcome MCR by disrupting tumor cell communication, potentially offering a new therapeutic strategy.
Area of Science:
- Oncology
- Cancer Biology
- Drug Resistance
Background:
- Multidrug resistance (MDR) research has dominated cancer treatment for two decades without clinical breakthroughs.
- Cancer cells in spheroids exhibit multicellular resistance (MCR), mirroring tumor characteristics in patients.
- MCR mechanisms include contact resistance, spheroid structure, apoptosis inhibition, quiescent cells, altered protein expression, and hypoxia.
Purpose of the Study:
- To investigate multicellular resistance (MCR) as a key challenge in cancer treatment.
- To explore novel therapeutic strategies beyond traditional multidrug resistance (MDR) approaches.
- To evaluate hyaluronidase as a potential agent to overcome MCR.
Main Methods:
- Analysis of MCR mechanisms in cancer spheroids.
- Review of therapeutic agents targeting cell-environment interactions.
- Investigation of hyaluronidase's role in drug penetration and MCR.
Main Results:
- MCR involves complex mechanisms distinct from MDR.
- Compounds disrupting tumor cell-microenvironment interactions show promise in preclinical models.
- Hyaluronidase, previously thought to enhance drug penetration, is hypothesized to decrease MCR.
Conclusions:
- A new class of drugs targeting MCR is needed.
- Disrupting tumor cell communication may circumvent MCR and inhibit metastasis.
- Hyaluronidase could be the first therapeutic agent in this new class, reducing MCR.