Recent submissions
Now showing items 321-340 of 658
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Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials.
(AMER ASSOC CANCER RESEARCH, 2020-09-15)PURPOSE: Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. PATIENTS AND METHODS: A ... -
Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation.
(SPRINGER, 2020-04-13)INTRODUCTION: To generate biomarkers of target engagement or predictive response for multi-target drugs is challenging. One such compound is the multi-AGC kinase inhibitor AT13148. Metabolic signatures of selective signal ... -
Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.
(BMJ PUBLISHING GROUP, 2020-03-01)BACKGROUND: This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge. CASE PRESENTATION: A 77-year-old woman with advanced epithelioid ... -
Radiological Evaluation of Newly Diagnosed Non-Brainstem Pediatric High-Grade Glioma in the HERBY Phase II Trial.
(AMER ASSOC CANCER RESEARCH, 2020-04-15)PURPOSE: The HERBY trial evaluated the benefit of the addition of the antiangiogenic agent Bevacizumab (BEV) to radiotherapy/temozolomide (RT/TMZ) in pediatric patients with newly diagnosed non-brainstem high-grade glioma ... -
Loss of 5'-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness.
(MDPI, 2020-02-20)The 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains ... -
CHK1 Inhibition Is Synthetically Lethal with Loss of B-Family DNA Polymerase Function in Human Lung and Colorectal Cancer Cells.
(AMER ASSOC CANCER RESEARCH, 2020-04-15)Checkpoint kinase 1 (CHK1) is a key mediator of the DNA damage response that regulates cell-cycle progression, DNA damage repair, and DNA replication. Small-molecule CHK1 inhibitors sensitize cancer cells to genotoxic ... -
Theranostic Attributes of Acoustic Cluster Therapy and Its Use for Enhancing the Effectiveness of Liposomal Doxorubicin Treatment of Human Triple Negative Breast Cancer in Mice.
(FRONTIERS MEDIA SA, 2020-02-20)INTRODUCTION: Acoustic cluster therapy (ACT) comprises co-administration of a formulation containing microbubble/microdroplet clusters (PS101), together with a regular medicinal drug (e.g., a chemotherapeutic) and local ... -
Therapeutic Dose Response of Acoustic Cluster Therapy in Combination With Irinotecan for the Treatment of Human Colon Cancer in Mice.
(FRONTIERS MEDIA SA, 2019-11-19)Introduction: Acoustic Cluster Therapy (ACT) comprises coadministration of a formulation containing microbubble-microdroplet clusters (PS101) together with a regular medicinal drug and local ultrasound (US) insonation of ... -
Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.
(AMER ASSOC CANCER RESEARCH, 2020-07-01)Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases ... -
A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.
(ELSEVIER, 2020-02-21)BACKGROUND: Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence ... -
Selection and Characterization of a Nanobody Biosensor of GTP-Bound RHO Activities.
(MDPI, 2019-01-09)RHO (Ras HOmologous) GTPases are molecular switches that activate, in their state bound to Guanosine triphosphate (GTP), key signaling pathways, which involve actin cytoskeleton dynamics. Previously, we selected the nanobody ... -
Small-molecule targeting of brachyury transcription factor addiction in chordoma.
(2019-02)Chordoma is a primary bone cancer with no approved therapy 1 . The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in ... -
Cancer cell killing by target antigen engagement with engineered complementary intracellular antibody single domains fused to pro-caspase3.
(NATURE PORTFOLIO, 2019-06-12)Many tumour causing proteins, such as those expressed after chromosomal translocations or from point mutations, are intracellular and are not enzymes per se amenable to conventional drug targeting. We previously demonstrated ... -
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.
(NATURE PUBLISHING GROUP, 2019-06-13)Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that ... -
Diverse AR Gene Rearrangements Mediate Resistance to Androgen Receptor Inhibitors in Metastatic Prostate Cancer.
(AMER ASSOC CANCER RESEARCH, 2020-04-15)PURPOSE: Prostate cancer is the second leading cause of male cancer deaths. Castration-resistant prostate cancer (CRPC) is a lethal stage of the disease that emerges when endocrine therapies are no longer effective at ... -
The kinase polypharmacology landscape of clinical PARP inhibitors.
(NATURE PORTFOLIO, 2020-02-17)Polypharmacology plays an important role in defining response and adverse effects of drugs. For some mechanisms, experimentally mapping polypharmacology is commonplace, although this is typically done within the same protein ... -
Applications of liquid biopsies in metastatic castration resistant prostate cancer
(Institute of Cancer Research (University Of London), 2020-02-29)Despite many recent advances, treating advanced prostate cancer (PC) remains clinically challenging. The need for vaildated circulating biomarkers is well recognised in almost all cancers, including in PC. Whilst circulating ... -
Combining large scale in silico analysis with fragment screening to identify novel, ligandable secondary sites in cancer-associated proteins
(Institute of Cancer Research (University Of London), 2020-01-31)Proteins often have multiple binding sites involved in interactions with other molecules. The majority of currently approved drugs bind a protein's primary site, the major functional site in the protein. Targeting the ... -
Genomics of lethal prostate cancer at diagnosis and castration resistance.
(AMER SOC CLINICAL INVESTIGATION INC, 2020-04-01)The genomics of primary prostate cancer differ from those of metastatic castration-resistant prostate cancer (mCRPC). We studied genomic aberrations in primary prostate cancer biopsies from patients who developed mCRPC, ...