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Updated: Mar 23, 2026

A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer
Francesco Pappalardo1, Giulia Russo1, Saverio Candido2
1Department of Drug Sciences, University of Catania, 95125, Catania, Italy.
Background:
Malignant melanoma is an aggressive tumor of the skin and seems to be resistant to current therapeutic approaches. Melanocytic transformation is thought to occur by sequential accumulation of genetic and molecular alterations able to activate the Ras/Raf/MEK/ERK (MAPK) and/or the PI3K/AKT (AKT) signalling pathways. Specifically, mutations of B-RAF activate MAPK pathway resulting in cell cycle progression and apoptosis prevention. According to these findings, MAPK and AKT pathways may represent promising therapeutic targets for an otherwise devastating disease.
Result:
Here we show a computational model able to simulate the main biochemical and metabolic interactions in the PI3K/AKT and MAPK pathways potentially involved in melanoma development. Overall, this computational approach may accelerate the drug discovery process and encourages the identification of novel pathway activators with consequent development of novel antioncogenic compounds to overcome tumor cell resistance to conventional therapeutic agents. The source code of the various versions of the model are available as S1 Archive.
Insights
This study introduces a computational model to simulate key pathways in melanoma development. This approach aims to accelerate drug discovery for novel anti-cancer compounds to combat treatment resistance.
Area of Science:
- Computational biology
- Oncology
- Biochemistry
Background:
- Malignant melanoma is an aggressive skin cancer resistant to current therapies.
- Melanoma development involves genetic alterations activating the MAPK and PI3K/AKT signaling pathways.
- B-RAF mutations activate the MAPK pathway, promoting cell cycle progression and preventing apoptosis.
Purpose of the Study:
- To develop a computational model simulating biochemical and metabolic interactions in melanoma-related signaling pathways.
- To identify potential therapeutic targets within the MAPK and PI3K/AKT pathways.
- To accelerate the discovery of novel anti-cancer compounds for melanoma treatment.
Main Methods:
- Development of a computational model to simulate PI3K/AKT and MAPK signaling pathways.
- Analysis of biochemical and metabolic interactions within these pathways relevant to melanoma.
- Utilizing computational simulation to explore pathway dynamics.
Main Results:
- A computational model was successfully developed to simulate key interactions in the PI3K/AKT and MAPK pathways.
- The model provides a platform for understanding melanoma development at a molecular level.
- The source code for the model is available for further research.
Conclusions:
- Computational modeling offers a promising approach to accelerate drug discovery for melanoma.
- The developed model can aid in identifying novel pathway activators and anti-cancer compounds.
- This strategy may help overcome tumor cell resistance to conventional therapies.
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