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Updated: Aug 7, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Chemosensitivity testing as an aid to anti-cancer drug and regimen development
1Translational Oncology Research Centre, Department of Histopathology, Queen Alexandra Hospital, Portsmouth, PO6 3LY, UK. ian.cree@port.ac.uk
Abstract:
The ATP-based chemosensitivity assay has proved particularly useful for the evaluation of new anti-cancer agents and combinations. The majority of our publications in this area have concentrated on topoisomerase inhibitors. Comparison of mitoxantrone with doxorubicin convinced us that these two agents were not completely cross-resistant and led to the design of the mitoxantrone + paclitaxel regimen which is now in clinical practice. Re-assessment of treosulfan in uveal melanoma led to the design of a new regimen combining this alkylating agent with gemcitabine, again with rapid introduction of this combination to clinical practice. The assay has recently been used to examine the concentration-activity curve to determine which tumours might benefit from liposomal preparations capable of delivering 4-16 times the standard dose without cardiotoxicity. Assay-directed use of Caelyx is producing encouraging results, and we are now examining this drug in combination with others. We recently showed that XR5000, a combined inhibitor of topoisomerase I and II, was effective against melanoma as well as ovarian cancer, but at concentrations which were unlikely to be achieved in patients. These data confirm our suggestion that use of the assay could reduce the time to introduction of new anti-cancer drugs and the cost of this process.
Insights
The ATP-based chemosensitivity assay accelerates the development of new anti-cancer drugs and combinations. This method aids in identifying effective cancer treatments, reducing development time and costs.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- The ATP-based chemosensitivity assay is a valuable tool for evaluating novel anti-cancer agents.
- Previous research focused on topoisomerase inhibitors, leading to clinical advancements.
Purpose of the Study:
- To assess the utility of the ATP-based chemosensitivity assay in drug development.
- To explore novel anti-cancer drug combinations and formulations.
Main Methods:
- Utilized the ATP-based chemosensitivity assay to evaluate anti-cancer agents and combinations.
- Investigated drug concentration-activity relationships for liposomal preparations.
- Assessed novel compounds like XR5000, a dual topoisomerase inhibitor.
Main Results:
- Identified non-cross-resistance between mitoxantrone and doxorubicin, leading to the mitoxantrone + paclitaxel regimen.
- Re-evaluation of treosulfan informed a new combination regimen with gemcitabine for uveal melanoma.
- Assay-directed use of liposomal Caelyx shows promise, with ongoing combination studies.
- XR5000 demonstrated efficacy in melanoma and ovarian cancer, though at potentially unachievable concentrations.
Conclusions:
- The ATP-based chemosensitivity assay effectively guides the development and clinical introduction of new anti-cancer therapies.
- This assay has the potential to significantly reduce the time and cost associated with anti-cancer drug development.
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