Biology subjects

Jonas, O.

Publications and source records attributed to Jonas, O..

3 recordsLinked to original sources

bioRxiv2026

An in vivo platform to jointly monitor cellular and metabolic responses to chemotherapy.

How drug treatments reshape immune and metabolic states within intact tumors remains difficult to study with existing methods. We introduce a spatial pharmacology platform that enables parallel analysis of multiple agents within a single tumor, linking local drug exposure to immune and metabolic remodeling. Using a microdevice for localized drug delivery, we created a large-scale paired CyCIF-MALDI dataset spanning 1.5 million cells across 27 MMTV-PyMT tumor sections and nine treatment programs, enabling integrated spatial pharmacology at unprecedented scale. Metabolic signatures robustly predict proteomic spatial neighborhoods establishing metabolism as a powerful predictor of tumor organization and immune phenotype. Within this framework, we identify a dominant metabolic axis defined by the myeloid polarization between CSF1R+ tumor-associated macrophages and MPO+ infiltrating myeloid cells localized near regions of drug-induced tumor cell death. Finally, we detect putative lipid-associated macrophage (LAM)-like populations within drug-resistant treatment regions.

bioengineering↗

bioRxiv2022

Polo-like kinase-1 Inhibitors and the Antiandrogen Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling

Abiraterone, a standard treatment for metastatic castrate-resistant prostate cancer (mCRPC), slows disease progression by abrogating androgen synthesis and antagonizing the androgen receptor (AR). We report that inhibitors of the mitotic kinase Plk1, including the clinically active third-generation Plk1 inhibitor onvansertib, when co-administered with abiraterone, synergistically kill cancer cells from a wide variety of tumor types in an androgen-independent manner, both in vitro and in vivo. Abiraterone treatment alone results in defects in mitotic spindle orientation, failure of complete chromosome condensation, and upregulation of mitosis and mitotic-spindle related gene sets independently of its effects on AR signaling. These effects, while mild following abiraterone monotherapy, result in profound sensitization to the anti-mitotic effects of Plk1 inhibition, leading to spindle assembly checkpoint-dependent mitotic cell death and entosis. In a murine PDX model of mCRPC, combined onvansertib and abiraterone resulted in enhanced mitotic arrest and dramatic inhibition of tumor cell growth compared to either agent alone. STATEMENT OF SIGNIFICANCEA phase 2 clinical trial is underway (NCT03414034) testing combined Plk1 inhibitor onvansertib and abiraterone in mCRPC patients with nascent abiraterone resistance. Our work establishes a mechanistic basis for that trial and indicates that combined abiraterone and onvansertib co-treatment may have broad utility for cancer treatment beyond mCRPC.

cancer biology↗

bioRxiv2021

Multiplex spatial systems analysis of local nanodose drug responses predicts effective treatment combinations of immunotherapies and targeted agents in mammary carcinoma

Better methods are needed to identify effective combinations of immunotherapies with chemotherapies and targeted anti-cancer agents. Here we present a Multiplex Implantable Microdevice Assay (MIMA) system for rapid in vivo assessment of the effects of multiple, spatially separate anticancer drugs directly in the complex tumor microenvironment. In prototypic experiments, olaparib, lenvatinib, palbociclib, venetoclax, panobinostat, doxorubicin, and paclitaxel and combinations thereof were administered simultaneously to murine mammary tumor models. Quantitative multiplex immunohistochemistry and spatial systems analyses of each local drug response defined cellular relations of fibroblasts, endothelial cells, immune lineages, immunogenic cell death, tumor proliferation and/or cancer stem cells that were used to predict effective drug combinations. A predicted combination of panobinostat, venetoclax and anti-CD40 showed long-term anti-tumor efficacy in multiple mouse models with no observable toxicity when administered systemically. Future MIMA use promises to design effective drug combinations for tumor cell control and immune activation on a personalized basis.

cancer biology↗