Speaker
Description
Cellular plasticity – the ability of cells to adapt to environmental changes by producing diverse phenotypes – plays a vital role in the reprogramming of cells across a broad spectrum of diseases, including cancer, diabetes, and neurodegeneration. It is also a key component of embryonic development and tissue remodelling. Targeting this plasticity is a promising therapeutic approach, as demonstrated by sequential and differentiation therapies, drug holidays, and alternating treatments \cite{kerestely_modulation_2026}.
An effective way to model complex cellular processes like plasticity is through network representations, such as protein–protein interaction (PPI) networks, signalling networks, and gene regulatory networks, whose network plasticity reflects cellular plasticity.
We aim to identify proteins that modulate network plasticity and elucidate their roles within the molecular networks of diseased cells. From the literature, we have gathered multiple regulators of network plasticity and cross-referenced these with existing drug targets. Our analysis indicates that intrinsically disordered proteins, a source of molecular-level plasticity, are enriched among regulators of network plasticity. The results of the network analysis suggest that direct signalling interactions involving network plasticity regulators are generally transient or causational, such as phosphorylation and transcriptional activation.
Bibliography
@article{kerestely_modulation_2026,
title = {Modulation of {Network} {Plasticity} {Opens} {Novel} {Therapeutic} {Possibilities} in {Cancer}, {Diabetes}, and {Neurodegeneration}},
volume = {13},
issn = {2198-3844, 2198-3844},
url = {https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202522532},
doi = {10.1002/advs.202522532},
abstract = {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.},
language = {en},
number = {12},
urldate = {2026-03-16},
journal = {Advanced Science},
author = {Kerestély, Márk and Narozsny, István and Szarka, Levente and Veres, Daniel V. and Csermely, Peter and Keresztes, Dávid},
month = feb,
year = {2026},
pages = {e22532},
}
