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Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration
Márk Kerestély1, István Narozsny1, Levente Szarka1
1Department of Molecular Biology, Semmelweis University, Budapest, Hungary.
Abstract:
Cellular plasticity is crucially important in cancer-induced cell reprogramming, as well as in regeneration therapies in diabetes, Alzheimer's, and Parkinson's diseases. Protein-protein interaction, signaling, and gene regulatory networks are increasingly used to describe plasticity-induced cellular adaptation in disease progression. This review delineates how network analysis of cell plasticity leads to novel therapy options against 1) cancer progression; 2) epithelial-mesenchymal transition-induced metastases; 3) cancer stem cells, and 4) pre-existent drug-resistant cells. Network plasticity-designed sequential and differentiation therapies are also outlined. 55 plasticity-related cancer drug targets are listed, where 20 have already approved drugs, 9 have investigational drugs, and 26 are drug target candidates. The recent expansion of plastic network-driven pancreatic beta cell and neuron regeneration therapies is described in diabetes, as well as in Alzheimer's and Parkinson's diseases, respectively. Finally, six major network-related research gaps and promising future research areas are outlined, including the discovery of plasticity-related cancer signaling pathways and cross-talks, cancer resensitization therapies, and the use of recently available proteome-wide network data and models to find novel cancer cell differentiation cocktails, drug targets, proper timing, and biomarkers of sequential therapies, as well as to perform in silico drug combination screens and in silico clinical trials.
Insights
Cellular plasticity networks offer new therapeutic strategies for cancer and neurodegenerative diseases. Network analysis reveals targets for drug development and regenerative medicine, improving patient outcomes.
Area of Science:
- Biochemistry
- Systems Biology
- Oncology
Background:
- Cellular plasticity is vital for cancer progression and regenerative medicine in diseases like diabetes, Alzheimer's, and Parkinson's.
- Network analysis of protein-protein interactions, signaling, and gene regulation describes cellular adaptation in disease.
- Understanding these networks is key to developing novel therapeutic interventions.
Purpose of the Study:
- To review how network analysis of cellular plasticity can inform novel therapeutic strategies.
- To highlight plasticity-related drug targets and regenerative therapies.
- To identify research gaps and future directions in network-based plasticity research.
Main Methods:
- Literature review focusing on network analysis of cellular plasticity.
- Identification and categorization of plasticity-related cancer drug targets.
- Description of network plasticity-designed therapies for cancer and regenerative medicine.
Main Results:
- Network analysis provides novel therapeutic options for cancer progression, metastasis, cancer stem cells, and drug resistance.
- 55 plasticity-related cancer drug targets were identified, with 20 approved drugs and 9 investigational drugs.
- Network-driven regenerative therapies for pancreatic beta cells and neurons show recent expansion.
Conclusions:
- Network analysis of cellular plasticity is a promising approach for developing innovative therapies.
- Further research into plasticity-related signaling pathways, drug resensitization, and computational modeling is warranted.
- Identifying biomarkers and optimizing sequential therapies through network-based approaches will advance clinical applications.
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