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Exploiting evolutionary steering to induce collateral drug sensitivity in cancer.
(NATURE PORTFOLIO, 2020-04-21)
Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another ...
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 ...
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 ...
A risk-based approach to experimental early phase clinical trials during the COVID-19 pandemic.
(ELSEVIER SCIENCE INC, 2020-07-01)
Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial.
(NATURE PORTFOLIO, 2023-07-25)
All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers the potential for enhanced effector cell potency. Here we report a Phase I dose ...
Clinical trial designs for evaluating and exploiting cancer evolution.
(ELSEVIER SCI LTD, 2023-07-01)
The evolution of drug-resistant cell subpopulations causes cancer treatment failure. Current preclinical evidence shows that it is possible to model herding of clonal evolution and collateral sensitivity where an initial ...
A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.
(AMER ASSOC CANCER RESEARCH, 2023-01-17)
PURPOSE: This was a Phase I/II trial of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 given in combination with gemcitabine. Its objectives were to establish the safety profile, recommended Phase 2 dose (RP2D), ...
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 ...
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 ...