Biology subjects

Munteanu, P.

Publications and source records attributed to Munteanu, P..

3 recordsLinked to original sources

bioRxiv2026

Artesunate Exploits Glutathione-Dependent Redox Vulnerability in Metastatic Lung Adenocarcinoma

Metastatic dissemination remains the principal cause of mortality in lung adenocarcinoma. To identify metabolic vulnerabilities associated with metastasis, we used cell lines with distinct metastatic abilities derived from the KrasG12D;p53KO mouse model. Building on evidence of mitochondrial dysfunction in metastasis-derived cells, we performed an in vivo screen of a focused metabolic drug library using a multiplexed DNA-barcoding platform. This approach identified artesunate as a selective inhibitor of metastatic seeding, which was validated in vivo to reduce metastatic burden while leaving primary tumor growth unaffected. Mechanistically, artesunate induced oxidative stress, characterized by reactive oxygen species and lipid peroxidation. Transcriptomic and mechanistic profiling revealed altered redox homeostasis in metastasis-derived cells. Inhibition of glutathione synthesis specifically sensitized these cells to artesunate, resulting in extensive cell death, whereas primary tumor-derived cells remained resistant. These findings identify glutathione-dependent redox homeostasis as a metabolic vulnerability in metastatic cells that can be specifically targeted using artesunate.

cancer biology↗

bioRxiv2026

Loss of the Y chromosome drives epigenetic and transcriptomic plasticity in lung adenocarcinoma

Loss of the Y chromosome (LOY) is associated with poor survival across multiple solid tumors, yet the underlying molecular mechanisms remain poorly understood. Here, we identify LOY as a central driver of lineage plasticity and epigenetic heterogeneity in lung adenocarcinoma. Integrating multi-omic profiling of primary samples with isogenic cellular models, we show that LOY triggers epithelial-to-mesenchymal transition (EMT). Mechanistically, LOY causes haploinsufficiency of dosage-sensitive regulators, leading to widespread DNA hypomethylation at EMT gene promoters, including THY1 and LOX. Single-cell multi-omic analyses demonstrate that LOY induces epigenetic heterogeneity, destabilizes the chromatin landscape, and increases lineage plasticity, enabling rapid cellular adaptation to metabolic and genotoxic stress. Moreover, LOY-induced plasticity facilitates tumor engraftment and metastatic dissemination in vivo. These findings establish Y-linked gene dosage as a critical guardian of epigenetic stability, providing a mechanistic rationale for how its loss amplifies phenotypic diversity and lineage plasticity, ultimately driving adverse clinical outcomes in LOY patients.

cancer biology↗

bioRxiv2026

Quantifying Treatment Resistance in Mixtures of Gastrointestinal Stromal Tumor Cells with BARMIX

Targeted therapies in gastrointestinal stromal tumors (GIST) often fail due to heterogeneous resistance mutations arising across metastatic sites. Efficient, rational design of mutation-specific therapies requires the ability to quantify treatment resistance across many genotypes in parallel. Here, we present BARcode MIXture analysis (BARMIX), a platform combining multiplexed experiments with DNA-barcoded cancer cell mixtures in vitro and in vivo, and a probabilistic framework for quantitative assessment of genotype-specific treatment resistance. BARMIX efficiently and accurately recapitulated known clinical resistance patterns in GIST and matched resistance measurements from individual cell lines in vitro and in vivo. This experimental-computational approach provides a scalable and broadly applicable strategy for quantifying treatment responses in complex cell populations, enabling systematic preclinical testing of new drugs and combinations to identify mutation-specific therapeutic options for precision oncology in GIST and beyond.

systems biology↗