A5040110214- Estrogen and related hormone effects
- FOXO transcription factor regulation
- Neuroblastoma Research and Treatments
- Lung Cancer Treatments and Mutations
- Telomeres, Telomerase, and Senescence
- Cancer Mechanisms and Therapy
- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- Nanoplatforms for cancer theranostics
- Cancer Immunotherapy and Biomarkers
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Pancreatic and Hepatic Oncology Research
- Adenosine and Purinergic Signaling
- Cancer, Lipids, and Metabolism
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Circular RNAs in diseases
- Histone Deacetylase Inhibitors Research
Sunesis (United States)
2021-2025
University of Turku
2005-2023
Åbo Akademi University
2005-2023
Molecular Oncology (United States)
2014-2023
Translational Research in Oncology
2022
Genentech
2015
NorthShore University HealthSystem
2015
Decatur Memorial Hospital
2015
UCSF Helen Diller Family Comprehensive Cancer Center
2009-2014
University of California, San Francisco
2008-2014
Abstract With only a fraction of patients responding to cancer immunotherapy, better understanding the entire tumor microenvironment is needed. Using single-cell transcriptomics, we chart fibroblastic landscape during pancreatic ductal adenocarcinoma (PDAC) progression in animal models. We identify population carcinoma-associated fibroblasts (CAF) that are programmed by TGFβ and express leucine-rich repeat containing 15 (LRRC15) protein. These LRRC15+ CAFs surround islets absent from normal...
Sonic hedgehog (SHH), an activating ligand of smoothened (SMO), is overexpressed in > 70% pancreatic cancers (PCs). We investigated the impact vismodegib, SHH antagonist, plus gemcitabine (GV) or placebo (GP) a multicenter phase Ib/randomized II trial and preclinical PC models.
T cell-retargeting therapies have transformed the therapeutic landscape of oncology. Regardless modality, cell activating are commonly accompanied by systemic cytokine release, which can progress to deadly release syndrome (CRS). Because incomplete mechanistic understanding relationship between activation and optimal toxicity management that retains full potential remains unclear. Here, we report type-specific cellular mechanisms link CD3 bispecific antibody-mediated killing toxic release....
BackgroundCancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that stabilizes the c-Myc (MYC) protein. However, clinical relevance CIP2A to cancers had not been demonstrated, but mechanism its regulation and role in cancer were completely unknown.
Cancer stem cells (CSCs) are hypothesized to actively maintain tumors similarly how their normal counterparts replenish differentiated cell types within tissues, making them an attractive therapeutic target for the treatment of cancer. Because most CSC markers also label tissue cells, it is unclear selectively without compromising homeostasis. We evaluated a strategy that targets surface leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), well-characterized and marker, with...
KRAS- and BRAF-mutant tumors are often dependent on MAPK signaling for proliferation survival thus sensitive to pathway inhibitors. However, clinical studies have shown that MEK inhibitors not uniformly effective in these cancers indicating mutational status of oncogenes does accurately capture activity. A number transcripts regulated by this recurrently identified genome-based transcriptional signatures. To test whether the output only 10 targets could quantify activity with potential...
Abstract Clinical results from the latest strategies for T-cell activation in cancer have fired interest combination immunotherapies that can fully engage immunity. In this study, we describe a trastuzumab-based bispecific antibody, HER2-TDB, which targets HER2 and conditionally activates T cells. HER2-TDB specifically killed HER2-expressing cells at low picomolar concentrations. Because of its unique mechanism action, is independent signaling or chemotherapeutic sensitivity, eliminated...
Senescence induction contributes to cancer therapy responses and is crucial for p53-mediated tumor suppression. However, whether p53 inactivation actively suppresses senescence has been unclear. Here, we show that E2F1 overexpression, due or p21 inactivation, promotes expression of human oncoprotein CIP2A, which in turn, by inhibiting PP2A activity, increases stabilizing serine 364 phosphorylation E2F1. Several lines evidence increased activity E2F1-CIP2A feedback renders breast cells...
The kinase RIP1 acts in multiple signaling pathways to regulate inflammatory responses and it can trigger both apoptosis necroptosis. Its activity has been implicated a range of inflammatory, neurodegenerative, oncogenic diseases. Here, we explore the effect inhibiting genetically, using knock-in mice that express catalytically inactive D138N, or pharmacologically, murine-potent inhibitor GNE684. Inhibition reduced collagen antibody-induced arthritis, prevented skin inflammation caused by...
Alveolar type II (AT2) cell dysfunction contributes to a number of significant human pathologies including respiratory distress syndrome, lung adenocarcinoma, and debilitating fibrotic diseases, but the critical transcription factors that maintain AT2 identity are unknown. Here we show E26 transformation-specific (ETS) family factor Etv5 is essential identity. Deletion from cells produced gene protein signatures characteristic differentiated alveolar I (AT1) cells. Consistent with defect in...
Granulocyte-colony stimulating factor (G-CSF) promotes mobilization of CD11b + Gr1 myeloid cells and has been implicated in resistance to anti-VEGF therapy mouse models. High G-CSF production associated with a poor prognosis cancer patients. Here we show that activation the RAS/MEK/ERK pathway regulates expression through Ets transcription factor. Several growth factors induced by MEK-dependent mechanism. Inhibition release MEK inhibitor markedly reduced vitro synergized antibodies reduce...
Purpose: The tumor microenvironment presents with altered extracellular matrix (ECM) and stroma composition, which may affect treatment efficacy contribute to tissue stiffness. Ultrasound (US) elastography can visualize quantify stiffness noninvasively. However, the contributions of ECM stromal components are poorly understood. We therefore set out density their relation stiffness.Experimental Design: A modified clinical ultrasound system was used measure perfusion during growth in...
Systemic cytokine release and on-target/off-tumor toxicity to normal tissues are the main adverse effects limiting clinical utility of T cell–redirecting therapies. This study was designed determine how binding affinity for CD3 tumor target HER2 impact efficacy nonclinical safety anti-HER2/CD3 cell–dependent antibodies (TDBs). Affinity found be a major determinant overall tolerability. Higher associated with rapidly elevated peripheral concentrations, weight loss in mice, poor tolerability...