A5007881635- Cancer Genomics and Diagnostics
- Mathematical Biology Tumor Growth
- Acute Myeloid Leukemia Research
- Evolution and Genetic Dynamics
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Gene Regulatory Network Analysis
- Chronic Lymphocytic Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Computational Drug Discovery Methods
- Multiple Myeloma Research and Treatments
- Immune cells in cancer
- Lung Cancer Treatments and Mutations
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Mathematical and Theoretical Epidemiology and Ecology Models
- Hippo pathway signaling and YAP/TAZ
- PI3K/AKT/mTOR signaling in cancer
- Advanced Breast Cancer Therapies
- thermodynamics and calorimetric analyses
- Malaria Research and Control
- Bioinformatics and Genomic Networks
Oslo University Hospital
2017-2025
Cleveland Clinic
2022-2024
University of Oslo
2018-2024
Cancer Registry of Norway
2023
Cleveland Clinic Lerner College of Medicine
2022
Norwegian Cancer Society
2013-2020
U-M Rogel Cancer Center
2019
Cancer Genetics (United States)
2017
Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy poorly understood. In this study, we investigate initial standard induction in cohort 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cytometry. Through supervised and unsupervised machine learning approaches, find that reduction extracellular-signal-regulated kinase (ERK) 1/2 p38 mitogen-activated protein (MAPK) phosphorylation cell compartment 24 h post-chemotherapy...
The evolution of resistance remains one the primary challenges for modern medicine, from infectious diseases to cancers. Many these resistance-conferring mutations often carry a substantial fitness cost in absence treatment. As result, we would expect mutants undergo purifying selection and be rapidly driven extinction. Nevertheless, preexisting is frequently observed drug-resistant malaria targeted cancer therapies non-small-cell lung (NSCLC) melanoma. Solutions this apparent paradox have...
Mutant selection windows (MSWs), the range of drug concentrations that select for drug-resistant mutants, have long been used as a model predicting resistance and designing optimal dosing strategies in infectious disease. The canonical MSW offers comparisons between two subtypes at time: drug-sensitive drug-resistant. In contrast, fitness landscape with N alleles, which maps genotype to fitness, allows genotypes simultaneously, but does not encode continuous response data. clinical settings,...
Background: Approximately 15%–20% of all diagnosed breast cancers are characterized by amplified and overexpressed HER2 (= ErbB2). These aggressive have a poor prognosis. Although improvements in treatment been achieved after the introduction trastuzumab lapatinib, many patients do not benefit from these drugs. Therefore, in-depth understanding mechanisms behind responses is essential to find alternative therapeutic strategies. Materials methods: Thirteen positive cancer cell lines were...
Abstract Tyrosine kinase inhibitors (TKI) have revolutionized treatment of oncogene-driven non-small cell lung cancer (NSCLC). However, almost all patients with advanced disease eventually acquire resistance and the remains largely incurable. Much research is dedicated to identifying targeting molecular mechanisms resistance. But even when challenged by our most treatments, cancers display a remarkable ability adapt. We seek complement development new agents investigating scheduling - dose...
Tumor heterogeneity is an important driver of treatment failure in cancer since therapies often select for drug-tolerant or drug-resistant cellular subpopulations that drive tumor growth and recurrence. Profiling the drug-response samples using traditional genomic deconvolution methods has yielded limited results, due part to imperfect mapping between variation functional characteristics. Here, we leverage mechanistic population modeling develop a statistical framework profiling phenotypic...
Abstract Theoretical and applied cancer studies that use individual-based models (IBMs) have been limited by the lack of a mathematical formulation enables rigorous analysis these models. However, spatial cumulant (SCMs), which arisen from theoretical ecology, describe population dynamics generated specific family IBMs, namely spatio-temporal point processes (STPPs). SCMs are spatially resolved formulated system differential equations approximate two STPP-generated summary statistics:...
Current treatment selection for acute myeloid leukemia (AML) patients depends on risk stratification based cytogenetic and genomic markers. However, the forecasting accuracy of response remains modest, with most receiving intensive chemotherapy. Recently, ex vivo drug screening has gained traction in personalized as a tool mapping patient groups relevant cancer dependencies. Here, we systematically evaluated use sensitivity profiling predicting survival clinical to chemotherapy cohort AML...
Abstract Integrating mathematical modeling and in vitro experiments to measure ecological interactions cancer Maximilian Strobl, Dagim Tadele, Jeffrey Maltas, Rowan Barker-Clarke, Mina Dinh, Jacob Scott Over the past two decades it has become clear that tumours are complex evolving ecosystems, which different cell populations interact with each other their non-tumour microenvironment. This understanding given rise intriguing idea we might be able leverage these slow, or even revert,...
Internal tandem duplications in the tyrosine kinase receptor FLT3 (FLT3-ITD) are among most common lesions acute myeloid leukemia and there exists a need for new forms of treatment.Using ex vivo drug sensitivity screening, we found that FLT3-ITD+ patient cells particularly sensitive to HSP90 inhibitors.While it is well known important FLT3-ITD stability, family members play much more complex role signaling than previously appreciated.First, activates unfolded protein response, leading...
ABSTRACT The evolution of resistance remains one the primary challenges for modern medicine from infectious diseases to cancers. Many these resistance-conferring mutations often carry a substantial fitness cost in absence treatment. As result, we would expect mutants undergo purifying selection and be rapidly driven extinction. Nevertheless, pre-existing is frequently observed drug-resistant malaria targeted cancer therapies non-small cell lung (NSCLC) melanoma. Solutions this apparent...
Breakpoint Cluster Region-Abelson kinase (BCR-Abl) is a driver oncogene that causes chronic myeloid leukemia and subset of acute lymphoid leukemias. Although tyrosine inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem cells (LSCs), the cancer-initiating compete with normal hematopoietic bone marrow niche. New strategies to target cancers driven by BCR-Abl are therefore urgently needed. We performed small molecule screen based on competition...
Selection upon intrinsic fitness differences is one of the most basic mechanisms evolution, fundamental to all biology. Equally, within macroscopic populations and microscopic environments, ecological interactions influence evolution. Direct experimental evidence selection between agents continues grow. Whilst eco-evolutionary dynamics describes how population composition, we build a model that allows aspects these fall on spectrum independent population. With our mathematical framework,...
Cell-cell fusion has been implicated in various physiological and pathological processes, including cancer progression. This study investigated the role of cell-cell non-small cell lung (NSCLC), focusing on its contribution to chemoresistance tumor evolution. By co-culturing drug-sensitive drug-resistant NSCLC lines, we observed spontaneous events, particularly under gefitinib selection. These fused cells exhibited enhanced fitness a higher degree compared parental lines across panel 12...
Tumor heterogeneity is a complex and widely recognized trait that poses significant challenges in developing effective cancer therapies. In particular, many tumors harbor variety of subpopulations with distinct therapeutic response characteristics. Characterizing this by determining the subpopulation structure within tumor enables more precise successful treatment strategies. our prior work, we developed PhenoPop, computational framework for unravelling drug-response from bulk...
Abstract Introduction: Pre-treatment tumor heterogeneity in cancer is a major driver of drug resistance. Given that resistance mechanisms often impose fitness cost, the presence drug-resistant clones prior to treatment poses paradox—less fit should be selected out growing population. Recent work has identified frequency-dependent interactions (FDIs) cell lines, where different proportions drug-sensitive and resistant cells modulate their respective fitness. FDIs may help explain...
Summary Tumor heterogeneity is an important driver of treatment failure in cancer since therapies often select for drug-tolerant or drug-resistant cellular subpopulations that drive tumor growth and recurrence. Profiling the drug-response samples using traditional genomic deconvolution methods has yielded limited results, due part to imperfect mapping between variation functional characteristics. Here, we leverage mechanistic population modeling develop a statistical framework profiling...
Abstract Background: A fundamental hallmark of cancer cells is their ability to sustain proliferative signaling and cell survival, reflected in a cellular chemotherapy response that poorly understood. We questioned whether modulated phospho-signaling at 4 24 h vivo could provide information about long-term survival acute myeloid leukemia (AML), if the therapy was more informative than analysis time diagnosis. Methods: Peripheral blood collected from 32 younger AML patients (age 16-74 years),...
Abstract Acute Myeloid Leukemia (AML) is a heterogeneous malignancy involving the clonal expansion of myeloid stem and progenitor cells in bone marrow peripheral blood. Most AML patients eligible for potentially curative treatment receive intensive chemotherapy. Risk stratification used to optimize intensity transplant strategy, mainly based on cytogenetic screening structural chromosomal alterations targeted sequencing selection common mutations. However, forecasting accuracy response...
Abstract About 15% of the diagnosed breast cancers have an amplicon in 17q12-21 region leading to over-expression human epidermal growth factor receptor 2 (HER2). HER2 activates two main downstream pathways, PI3K/Akt and MAPK that are involved survival, cell proliferation. positive (HER2+) treated with trastuzumab or lapatinib, which inhibit by different molecular mechanisms. However, many patients develop resistance do not respond treatment. Therefore, identification alternative compounds...