Related Experiment Video
Updated: May 3, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Activating adaptive cellular mechanisms of resistance following sublethal cytotoxic chemotherapy: implications for
Gregory T Wurz1, Michael W DeGregorio
1Division of Hematology and Oncology Department of Internal Medicine, University of California, Davis, Sacramento, CA.
Abstract:
As Phase 0 studies have proven to be reasonably predictive of therapeutic dose pharmacokinetics, the application of microdosing has expanded into metabolism, drug-drug interactions and now diagnostics. One potentially serious issue with this application of microdosing that has not been previously discussed is the possibility of activating cellular mechanisms of drug resistance. Here, we provide an overview of Phase 0 microdosing and drug resistance, with an emphasis on cisplatin resistance, followed by a discussion of the potential for inducing acquired resistance to platinum-based or other types of chemotherapy in cancer patients participating in Phase 0 diagnostic microdosing studies. A number of alternative approaches to diagnostic microdosing, such as the human tumor cloning assay and the use of peripheral blood mononuclear cells as a surrogate for measuring DNA adducts, are discussed that would avoid exposing cancer patients to low doses of first-line chemotherapy and the possible risk of triggering cellular mechanisms of acquired resistance. Until it has been established that diagnostic microdosing in cancer patients poses no risk of acquired drug resistance, such studies should be approached with caution.
Insights
Phase 0 microdosing, while useful for diagnostics, may trigger drug resistance mechanisms in cancer patients. Alternative diagnostic methods are recommended to avoid this risk and ensure patient safety.
Area of Science:
- Pharmacology
- Oncology
- Drug Resistance Mechanisms
Background:
- Phase 0 microdosing studies are increasingly used for pharmacokinetics, metabolism, drug-drug interactions, and diagnostics.
- A potential risk of microdosing, particularly in cancer patients, is the activation of cellular drug resistance mechanisms.
- Cisplatin resistance is a significant concern in oncology, and its potential induction by microdosing requires careful consideration.
Purpose of the Study:
- To review Phase 0 microdosing and its implications for drug resistance.
- To discuss the potential for diagnostic microdosing to induce acquired resistance to chemotherapy in cancer patients.
- To explore alternative diagnostic approaches that mitigate the risk of acquired drug resistance.
Main Methods:
- Overview of Phase 0 microdosing principles and applications.
- Analysis of cellular mechanisms of drug resistance, with a focus on platinum-based agents.
- Discussion of alternative diagnostic methods, including the human tumor cloning assay and peripheral blood mononuclear cell analysis.
Main Results:
- Phase 0 microdosing may inadvertently activate cellular mechanisms of drug resistance.
- Cancer patients undergoing diagnostic microdosing could develop acquired resistance to chemotherapy.
- Alternative methods offer potential to assess diagnostic markers without inducing drug resistance.
Conclusions:
- Diagnostic microdosing in cancer patients carries a potential risk of inducing acquired drug resistance.
- Alternative diagnostic strategies should be prioritized until the safety of microdosing is fully established.
- Caution is advised when implementing diagnostic microdosing studies in oncology settings.
More Related Videos
05:39Author Spotlight: Radiotherapy and Clonogenic Assays for Advancing Cancer Research and Personalized Medicine
Published on: April 5, 2024
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
Related Concept Videos
02:56Treatment Resistant Cancers
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
02:53Adaptive Mechanisms in Cancer Cells
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...