Biology subjects

Järvinen, P.

Publications and source records attributed to Järvinen, P..

2 recordsLinked to original sources

bioRxiv2026

Site-Dependent Decoupling of Drug-Biomarker Associations in Clear Cell Renal Cell Carcinoma Revealed by Functional Profiling of Patient-Derived Cell Models

Clear cell renal cell carcinoma (ccRCC) frequently exhibits primary and acquired resistance to standard-of-care therapies, underscoring the need for improved strategies to predict therapeutic response and prioritize patient-specific treatments. Although recent multi-omic and single-cell studies have provided insight into the molecular landscape of ccRCC, molecular alterations alone incompletely predict drug sensitivity. We prospectively profiled tumors from 28 patients with localized and metastatic ccRCC by integrating molecular characterization, functional drug sensitivity and resistance testing in patient-derived cell models, and longitudinal clinical data. Although genomic biomarkers suggested potentially actionable therapies in 27/28 patients, functional testing revealed discordance between genomic actionability and ex vivo drug sensitivity, whereas linear mixed-effects modelling uncovered 16 novel copy-number-based features associated with sensitivity to 11 drugs. Genotype-drug response associations were largely preserved between primary tumors and vena cava thrombi but frequently disrupted in distant metastases. Integrating functional drug testing with multi-omic profiling reveals vulnerabilities not apparent from genomic data alone, refines therapeutic actionability, captures interpatient and intersite heterogeneity in ccRCC, and provides a scalable framework for individualized treatment prioritization.

cancer biology↗

bioRxiv2024

Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses

Tumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of tumor immune microenvironment (TIME). Patient-derived ex vivo models contain authentic resident immune cells and therefore, could provide new mechanistic insights into how TIME responds to tumor or immune cell-directed therapies. Here, we assessed the reproducibility and robustness of immunomodulatory drug responses across two different ex vivo models of breast cancer TIME and one of renal cell carcinoma. These independently developed TIME models were treated with a panel of clinically relevant immunomodulators, revealing remarkably similar changes in gene expression and cytokine profiles among the three models in response to T cell activation and STING-agonism while still preserving individual patient-specific response patterns. Moreover, we found two common core signatures of adaptive or innate immune responses present across all three models and both types of cancer, potentially serving as a benchmark for drug-induced immune activation in ex vivo models of TIME. The robust reproducibility of immunomodulatory drug responses observed across diverse ex vivo models of TIME underscores the significance of human patient-derived models in elucidating the complexities of antitumor immunity and therapeutic interventions.

immunology↗