A5040064532- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Advanced Breast Cancer Therapies
- Monoclonal and Polyclonal Antibodies Research
- Melanoma and MAPK Pathways
- Cancer Mechanisms and Therapy
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Cancer Treatment and Pharmacology
- CAR-T cell therapy research
- Angiogenesis and VEGF in Cancer
- HER2/EGFR in Cancer Research
- Phagocytosis and Immune Regulation
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Lymphoma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Cutaneous Melanoma Detection and Management
- Glioma Diagnosis and Treatment
- Bladder and Urothelial Cancer Treatments
- Cognitive Computing and Networks
- Breast Cancer Treatment Studies
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
Henry Ford Hospital
2017
University of Zurich
2017
Genedata (Switzerland)
2017
Genentech
2001-2015
Fluidigm (United States)
2014
Health Awareness (United States)
2014
Computational Intelligence and Information Systems Lab
2014
University of Oxford
2011-2013
Array BioPharma (United States)
2013
MRC Weatherall Institute of Molecular Medicine
2011-2013
Exomes, transcriptomes and copy-number alterations in a sample of more than 70 primary human colonic tumours were analysed an attempt to characterize the genomic landscape; addition finding genes associated with commonly mutated signalling pathways, recurrent gene fusions involving R-spondin family members also found occur approximately 10% tumours, revealing potential new therapeutic target. An analysis exomes, colon matched normal controls has identified 35,000 protein-altering somatic...
Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required extend this benefit beyond subset patients. In preclinical models tumour-derived VEGF limits cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial activation. This study investigates how blockade with bevacizumab could potentiate PD-L1 inhibition atezolizumab mRCC....
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...
Purpose Vascular endothelial growth factor (VEGF) is a potent molecule that mediates tumor angiogenesis primarily through VEGF receptor 2 (VEGFR2). Bevacizumab, recombinant humanized monoclonal antibody to VEGF, was administered previously untreated patients evaluate parameters of angiogenesis. Patients and Methods Twenty-one with inflammatory locally advanced breast cancer were treated bevacizumab for cycle 1 (15 mg/kg on day 1) followed by six cycles doxorubicin (50 mg/m ) docetaxel (75...
Bevacizumab is a monoclonal antibody to vascular endothelial growth factor-A (VEGF). In the pivotal trial in metastatic colorectal cancer (mCRC), addition of bevacizumab first-line irinotecan, fluorouracil, and leucovorin (IFL) significantly prolonged median survival. The aim these retrospective subset analyses was evaluate VEGF, thrombospondin-2 (THBS-2), microvessel density (MVD) as prognostic factors and/or predictors benefit from bevacizumab.In trial, 813 patients with untreated mCRC...
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication immune system. Therapeutic use blocking antibodies to PD-L1 or its PD-1 has produced unparalleled, durable clinical responses, with highest likelihood response seen in patients whose tumour cells express before therapy. The significance expression each cell type emerged as a central and controversial unknown development immunotherapeutics. Using...
We describe the preclinical pharmacology and antitumor activity of GDC-0068, a novel highly selective ATP-competitive pan-Akt inhibitor currently in clinical trials for treatment human cancers.The effect GDC-0068 on Akt signaling was characterized using specific biomarkers pathway, response to evaluated cancer cell lines xenograft models with various genetic backgrounds, either as single agent or combination chemotherapeutic agents.GDC-0068 blocked both cultured tumor evidenced by...
Combinations of MAP/ERK kinase (MEK) and phosphoinositide 3-kinase (PI3K) inhibitors have shown promise in preclinical cancer models, leading to the initiation clinical trials cotargeting these two key signaling pathways. GDC-0973, a novel selective MEK inhibitor, GDC-0941, class I PI3K are early stage as both single agents combination. The discovery has allowed investigation into precise effects combining major branches downstream RAS. Here, we investigated multiple biomarkers...
Significance Programmed death-ligand 1 (PD-L1) expression on tumor cells and tumor-infiltrating immune is regulated by distinct mechanisms has nonredundant roles in regulating anticancer immunity, PD-L1 both cell types important for predicting best response to atezolizumab non-small lung cancer.
MPDL3280A is a human monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), and exerts anti-tumor activity mainly by blocking PD-L1 interaction with (PD-1) B7.1. It being investigated as potential therapy for locally advanced or metastatic malignancies. The purpose of the study reported here was to characterize pharmacokinetics, pharmacodynamics, tissue distribution tumor penetration and/or chimeric anti-PD-L1 PRO304397 help further clinical development. pharmacokinetics...
Abstract Close proximity between cytotoxic T lymphocytes and tumour cells is required for effective immunotherapy. However, what controls the spatial distribution of in microenvironment not well understood. Here we couple digital pathology transcriptome analysis on a large ovarian cohort develop machine learning approach to molecularly classify characterize tumour-immune phenotypes. Our study identifies two important hallmarks characterizing cell excluded tumours: 1) loss antigen...
Although immune checkpoint inhibitors (ICIs) are established as effective cancer therapies, overcoming therapeutic resistance remains a critical challenge. Here we identify interleukin 6 (IL-6) correlate of poor response to atezolizumab (anti-PD-L1) in large clinical trials advanced kidney, breast, and bladder cancers. In pre-clinical models, combined blockade PD-L1 the IL-6 receptor (IL6R) causes synergistic regression tumors substantially improves anti-tumor CD8+ cytotoxic T lymphocyte...
CD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading the hypothesis that their presence in tumors may predict response immunotherapy.Here, we test this combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled lung and bladder clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)).ITGAE was identified as most significantly...