Biology subjects

Cassoni, P.

Publications and source records attributed to Cassoni, P..

3 recordsLinked to original sources

bioRxiv2026

Ex vivo stem-like cell families model evolution of glioblastoma therapeutic resistance

Glioblastoma (GBM) arises from stem-like cells (GSCs) that exhibit intrinsic therapeutic resistance and can be positively selected by treatment, rendering recurrent GBM intractable. Mechanistic dissection of therapeutic resistance evolution has been limited by scarce matched primary/recurrent tractable models. To address this gap, we developed "resistant GSC families", a within-patient matched platform that models therapy-driven selection by ex vivo deriving, from the same primary whole GBM, temozolomide (TMZ)- and ionizing radiation (IR)-selected GSCs, alongside a treatment-naive control (CTRL-GSC). This design enables pressure-specific dissection of resistance evolution, separating chemotherapy- and radiotherapy-associated genetic alterations and adaptations that are often confounded in primary-versus-recurrent comparisons. Using this framework, we link TMZ-driven relapse-like states to either mismatch repair (MMR)-dependent stable resistance or O6-methylguanine-DNA methyltransferase (MGMT)-independent drug tolerance, and identify adaptive DNA damage response and cell-cycle changes as a route to increased radioresistance. Across pressures, treatment-emergent GSCs accumulate chromosomal alterations and exhibit adaptive phenotypic remodeling, including increased receptor tyrosine kinase activity. Resistant GSC families represent a model enabling mechanistic studies and hypothesis-driven testing of strategies aimed at preventing or treating GBM recurrence.

cancer biology↗

bioRxiv2025

The Pervasive Negative Regulation of Ion Channel Functional Families Across Human Cancers

The transmembrane transport of molecules and ions is fundamental to cellular homeostasis and coordination of physiological processes. During tumorigenesis, these processes undergo significant alterations in response to oncogenic transformations and microenvironmental pressures. However, a comprehensive systems-level characterization of transportome alterations across cancer types has been lacking. Here, we integrate structural, functional, and mechanistic annotations of all known human Ion Channels and Transporters (ICTs) into a curated database, organizing them into biologically coherent gene sets based on shared physiological and biophysical properties such as permeant species, gating mechanism, and transport directionality. By leveraging Gene Set Enrichment Analysis (GSEA) across transcriptomic profiles from 19 tumor types, we reveal a recurrent downregulation of ICTs--particularly ion channels--accompanied by selective upregulation of specific pump classes. Our findings uncover a conserved signature of transportome reprogramming in cancer and provide a quantitative framework for future integrative studies of ICT function. This work highlights both the complexity and plasticity of cellular transport systems in oncogenesis and offers a resource for modeling their roles in cancer systems biology.

cancer biology↗

bioRxiv2020

A drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent local relapse and treat established brain metastasis

Exclusion of brain metastases from clinical trials is a major cause of the limited therapeutic options for this growing population of cancer patients. Here, we report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to brain metastasis, we identified several hits from a library of FDA approved inhibitors and others being tested in clinical trials. A blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to organotypic cultures with metastases treated with the chaperone inhibitor revealed novel biomarkers in human brain metastasis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is fully compatible with human samples. We envision that METPlatform could be established as a clinically relevant strategy to personalize the management of metastatic disease in the brain and elsewhere. SummarySystemic spread of cancer continues to be the key aspect associated with lethality. In this publication, Zhu et al. describes a drug-screening platform specifically designed to study vulnerabilities of metastasis when colonizing secondary organs and demonstrates its value in difficult-to-treat brain metastasis using new models and patient-derived samples.

cancer biology↗