Andriy Marusyk

A reference-calibrated spatial-statistical framework for quantifying stroma-tumor cell spatial associations from histology and its geometric limits

This paper introduces a spatial-statistical framework to quantify stroma-tumor cell interactions from histology, showing geometric limits and applying it to identify proliferation bias in cancer.

Ploidy shapes gemcitabine response through altered potency and delayed cell death

This study shows that higher ploidy reduces gemcitabine potency and delays cell death by altering drug exposure kinetics and response timing.

Peristromal niches protect lung cancers from targeted therapies through a combined effect of multiple molecular mediators

This study shows that stromal niches protect lung cancers from ALK inhibitors through multiple mechanisms, and targeting these mechanisms together is more effective than targeting them individually.

Pharmacokinetic Acceleration via CYP3A4 Hyperactivation as a Clinically Actionable Mechanism of Targeted Therapy Resistance in NSCLC

This paper identifies CYP3A4 hyperactivation as a tumor-extrinsic resistance mechanism in NSCLC, showing it reduces drug exposure and leads to resistance, and proposes dosing optimization and CYP3A4 inhibition as solutions.

Selection for targeted therapy resistance leads to an indirect selection for higher phenotypic plasticity and enhanced evolvability to orthogonal stressors

The paper shows that targeted therapy resistance in cancer selects for cells with higher phenotypic plasticity, which enhances their ability to adapt to other stressors and promotes metastasis.

Mega-frequency mutagenesis: generation of non-random precise mutations with extremely high frequency upon adaptation of cancer cells to drugs and stress

The paper shows that cancer cells generate non-random, high-frequency mutations during drug adaptation, enriched near transcription factor binding sites.

Cancer-associated fibroblasts confer ALK inhibitor resistance in EML4-ALK-driven lung cancer via concurrent integrin and MET signaling

This study identifies that CAFs confer ALK inhibitor resistance in EML4-ALK-driven lung cancer through both MET and integrin signaling pathways, and shows that targeting both pathways improves treatment efficacy.

Evolutionary antifragile therapy

This paper develops and validates a treatment strategy called evolutionary antifragile therapy, which uses treatment fluctuations to limit tumor resistance evolution.

The adaptive state determines the impact of mutations on evolving populations

This study shows that mutation impacts on populations depend on their adaptive state, with increased mutation rates beneficial near extinction but harmful in well-adapted populations.

Trastuzumab deruxtecan combination strongly enhances responses and overcomes sotorasib resistance in KRASG12C-mutant NSCLC

This study shows that combining trastuzumab deruxtecan with sotorasib improves responses in KRASG12C-mutant NSCLC and overcomes resistance, but HER2 expression levels influence treatment effectiveness.

Cell-Cell Fusion in NSCLC Promotes Evolution of Therapeutic Resistance

This study shows that cell-cell fusion in NSCLC leads to increased chemoresistance and tumor aggressiveness by creating hybrid cells with enhanced fitness and genomic heterogeneity.

The impact of tumor stromal architecture on therapy response and clinical progression

This paper investigates how tumor stromal architecture influences therapy response and resistance in lung, breast, and kidney cancers using mathematical models, experimental studies, and clinical analysis.

Dark selection for JAK/STAT-inhibitor resistance in chronic myelomonocytic leukemia

The paper challenges the classic U-shape model of resistance by proposing alternative population-level models for ruxolitinib resistance in CMML and explores the role of oxygen and cytokine signaling in resistance dynamics.

Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer.

This study shows that resistance to ALK inhibitors in lung cancer is unstable and dynamic, with collateral sensitivity to other drugs offering new treatment options.

Harnessing the lymphocyte meta-phenotype to optimize adoptive cell therapy

This paper explores using a lymphocyte meta-phenotype to improve adoptive cell therapy outcomes by integrating patient data with mathematical models.