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Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
Published on: November 24, 2021
Skin equivalents: a tool for the discovery and validation of pharmacodynamic biomarkers
Chantal Paolini1, Angela Orecchia, Cristina M Failla
1Exiris s.r.l., Rome, Italy.
Abstract:
In the development of targeted oncology drugs, it is important to assess drug effectiveness in individual patients. We evaluated the possibility of reproducing in an ex-vivo system the biological effects observed in vitro and in vivo by the combined administration of two chemotherapeutic drugs, gemcitabine and a small inhibitor of Wee1. We found that modulation of both CDC2 phosphorylation and of a previously-identified gene signature was detectable in human skin equivalents obtained with primary keratinocytes from three individuals. Therefore, we suggest that human skin equivalents could represent a promising tool for the identification and validation of novel pharmacodynamic biomarkers.
Insights
Human skin equivalents can model the effects of combined chemotherapy drugs like gemcitabine and Wee1 inhibitors. This system shows promise for identifying new pharmacodynamic biomarkers in personalized oncology.
Area of Science:
- Oncology
- Pharmacology
- Biomarker Discovery
Background:
- Assessing targeted oncology drug effectiveness in individual patients is crucial.
- Combined drug administration requires robust methods for evaluating biological effects.
- Existing in vitro and in vivo models have limitations in predicting patient-specific responses.
Purpose of the Study:
- To evaluate the utility of an ex-vivo human skin equivalent system.
- To determine if this system can reproduce biological effects of combined gemcitabine and Wee1 inhibitor therapy.
- To explore the potential for identifying novel pharmacodynamic biomarkers.
Main Methods:
- Utilized human skin equivalents derived from primary keratinocytes of three individuals.
- Administered a combination of gemcitabine and a Wee1 inhibitor ex-vivo.
- Monitored modulation of CDC2 phosphorylation.
- Assessed changes in a previously identified gene signature.
Main Results:
- Modulation of CDC2 phosphorylation was detectable in the ex-vivo system.
- Changes in the specific gene signature were observed.
- The biological effects mirrored those seen in vitro and in vivo.
Conclusions:
- Human skin equivalents can successfully replicate key biological responses to combined chemotherapy.
- This ex-vivo model shows potential for identifying and validating new pharmacodynamic biomarkers.
- The system offers a promising avenue for personalized oncology drug development.
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