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Updated: Mar 19, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Evaluation of surrogate tissues as indicators of drug activity in a melanoma skin model
Palak R Parekh1,2, Rohini Choudhuri2,3, Urbain Weyemi2
1Department of Radiation Oncology, Greenbaum Cancer Center, School of Medicine, University of Maryland, Baltimore, Maryland.
Abstract:
The development of novel cancer treatments is a challenging task, partly because results from model systems often fail to predict drug efficacy in humans, and also tumors are often inaccessible for biochemical analysis, preventing effective monitoring of drug activity in vivo. Utilizing a model system, we evaluated the use of drug-induced DNA damage in surrogate tissues as indicators of drug efficacy. Samples of a commercially available melanoma skin model (Mattek MLNM-FT-A375) containing keratinocyte and fibroblast layers with melanoma nodules were subjected to various chemotherapeutic regimens for one, four, or eight days. At these times they were analyzed for DNA double-stranded breaks (γH2AX foci) and apoptosis (TUNEL). A wide range of drug responses in both tumor and normal tissues were observed and cataloged. For the melanoma, the most common drug response was apoptosis. The basal keratinocyte layer, which was the most reliable indicator of drug response in the melanoma skin model, responded with γH2AX foci formation that was abrupt and transient. The relationships between tumor and surrogate tissue drug responses are complex, indicating that while surrogate tissue drug responses may be useful clinical tools, careful control of variables such as the timing of sampling may be important in interpreting the results.
Insights
This study explored using DNA damage in skin cells as a reliable indicator of cancer drug effectiveness. Basal keratinocytes showed transient DNA damage, suggesting their potential as a surrogate tissue for monitoring treatment efficacy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Developing effective cancer treatments is hindered by poor prediction of drug efficacy from models and difficulty monitoring drug activity in tumors.
- Novel methods are needed to assess drug response in vivo, especially when tumors are inaccessible.
Purpose of the Study:
- To evaluate drug-induced DNA damage in surrogate tissues as a potential indicator of cancer drug efficacy.
- To analyze the response of a melanoma skin model to chemotherapy and identify reliable surrogate tissues for monitoring drug activity.
Main Methods:
- Utilized a commercially available melanoma skin model (Mattek MLNM-FT-A375) with melanoma nodules, keratinocytes, and fibroblasts.
- Treated the model with various chemotherapeutic regimens for 1, 4, or 8 days.
- Assessed DNA double-stranded breaks (γH2AX foci) and apoptosis (TUNEL assay) in tumor and normal tissue layers.
Main Results:
- Observed a wide range of drug responses in both melanoma and normal skin components.
- Melanoma primarily responded with apoptosis, while basal keratinocytes showed transient γH2AX foci formation.
- Basal keratinocytes emerged as the most reliable indicator of drug response within this melanoma skin model.
Conclusions:
- Drug-induced DNA damage in surrogate tissues, particularly basal keratinocytes, can serve as an indicator of cancer drug efficacy.
- The complex relationship between tumor and surrogate tissue responses necessitates careful control of variables, such as sampling time, for accurate interpretation.
- Surrogate tissue analysis holds promise as a clinical tool for monitoring cancer therapeutic effectiveness.
