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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 ...
Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity ...
A first-in-human phase I study of the PD-1 inhibitor, retifanlimab (INCMGA00012), in patients with advanced solid tumors (POD1UM-101).
(ELSEVIER, 2024-04-01)
BACKGROUND: Retifanlimab is a humanized, hinge-stabilized immunoglobulin G4κ monoclonal antibody against human programmed cell death protein 1 (PD-1). This first-in-human, phase I study assessed the safety and efficacy of ...
Abiraterone in "High-" and "Low-risk" Metastatic Hormone-sensitive Prostate Cancer.
(ELSEVIER, 2019-12-01)
BACKGROUND: Abiraterone acetate received licencing for use in only "high-risk" metastatic hormone-naïve prostate cancer (mHNPC) following the LATITUDE trial findings. However, a "risk"-related effect was not seen in the ...
Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma.
<h4>Purpose</h4>In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety ...
Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG).
<h4>Background</h4>Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are standard of care for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) with common mutations (Del19 or ...
Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells.
<h4>Purpose</h4>To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design.<h4>Experimental ...
Can patient decision aids reduce decisional conflict in a de-escalation of breast radiotherapy clinical trial? The PRIMETIME Study Within a Trial implemented using a cluster stepped-wedge trial design.
(2021-06-14)
<h4>Background</h4>For patients with early breast cancer considered at very-low risk of local relapse, risks of radiotherapy may outweigh the benefits. Decisions regarding treatment omission can lead to patient uncertainty ...
Increasing frequency of gene copy number aberrations is associated with immunosuppression and predicts poor prognosis in gastric adenocarcinoma.
<h4>Background</h4>Patients with Epstein-Barr virus-positive gastric cancers or those with microsatellite instability appear to have a favourable prognosis. However, the prognostic value of the chromosomal status ...
Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets.
(NATURE PUBLISHING GROUP, 2018-05-01)
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer ...