A5086692150- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Advanced Breast Cancer Therapies
- Immunodeficiency and Autoimmune Disorders
- PI3K/AKT/mTOR signaling in cancer
- Phagocytosis and Immune Regulation
- Protein Degradation and Inhibitors
Oslo University Hospital
2022-2024
University of Oslo
2022-2024
Increasing use of covalent and noncovalent inhibitors Bruton's tyrosine kinase (BTK) has elucidated a series acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance distinct enzymatic activities, including some that impair activity while imparting novel protein-protein interactions sustain receptor (BCR) signaling. Furthermore, describe clinical-stage IKZF1/3 degrader, NX-2127, can bind proteasomally degrade each mutant proteoform,...
The microenvironment of chronic lymphocytic leukemia (CLL) cells in lymph nodes, spleen, and bone marrow provides survival, proliferation, drug resistance signals. Therapies need to be effective these compartments, pre-clinical models CLL that are used test sensitivity must mimic the tumor reflect clinical responses. Ex vivo have been developed capture individual or multiple aspects microenvironment, but they not necessarily compatible with high-throughput screens. Here, we report on a model...
PI3K inhibitors (PI3Ki) are approved for relapsed chronic lymphocytic leukemia (CLL). Although patients may show an initial response to these therapies, development of treatment intolerance or resistance remain clinical challenges. To overcome these, prediction individual responses based on actionable biomarkers is needed. Here, we characterized the activity and cellular effects 10 PI3Ki investigated whether functional analyses can identify vulnerabilities in PI3Ki-refractory/intolerant CLL...
Background: Although targeted therapies have made a breakthrough in CLL treatment, many patients develop resistance, severe side effects, or relapse during treatment. Due to the wide heterogeneity both clinicobiological features and clinical outcomes, require personalized management strategies. HOVON 141/VISION is randomized phase II trial that evaluates efficacy of minimal residual disease (MRD) guided combinatorial treatment with Bcl-2 antagonist venetoclax BTK inhibitor ibrutinib...
ABSTRACT Purpose Phosphatidylinositol 3-kinase inhibitors (PI3Ki) are approved for relapsed chronic lymphocytic leukemia (CLL). While patients may show an initial response, development of treatment intolerance or resistance remains a clinically challenging. Prediction individual responses based on actionable biomarkers is needed to overcome these challenges. Here, we investigated whether ex vivo functional targeted therapies can stratify responders idelalisib and guide precision medicine in...
<div>AbstractPurpose:<p>PI3K inhibitors (PI3Ki) are approved for relapsed chronic lymphocytic leukemia (CLL). Although patients may show an initial response to these therapies, development of treatment intolerance or resistance remain clinical challenges. To overcome these, prediction individual responses based on actionable biomarkers is needed. Here, we characterized the activity and cellular effects 10 PI3Ki investigated whether functional analyses can identify vulnerabilities...
<div>AbstractPurpose:<p>PI3K inhibitors (PI3Ki) are approved for relapsed chronic lymphocytic leukemia (CLL). Although patients may show an initial response to these therapies, development of treatment intolerance or resistance remain clinical challenges. To overcome these, prediction individual responses based on actionable biomarkers is needed. Here, we characterized the activity and cellular effects 10 PI3Ki investigated whether functional analyses can identify vulnerabilities...
Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia
Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia
Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia
Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia
Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia
Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia
Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia
Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia
Background: The phosphatidylinositol 3-kinase inhibitors (PI3Ki) idelalisib and duvelisib are approved for relapsed chronic lymphocytic leukemia (CLL). While patients may show an initial response to these therapies, development of treatment resistance or intolerance remains clinical challenges. Prediction individual responses based on clinically actionable biomarkers is needed overcome Aims: 1. To characterize functional 10 PI3Ki in CLL 2. study drug class activity idelalisib-refractory 3....