73 research outputs found
Advances in using PARP inhibitors to treat cancer
The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents
Monitoring pharmacodynamic response to nucleoside analogs targeting DNMT1 using p16/INK4a re-expression in circulating tumor cells.
Targeting embryonic transcription factors to affect cancer stem cells and systemic therapy.
Translating pharmacodynamic biomarkers from bench to bedside: analytical validation and fit-for-purpose studies to qualify multiplex immunofluorescent assays for use on clinical core biopsy specimens
Preclinical Modeling of a Phase 0 Clinical Trial: Qualification of a Pharmacodynamic Assay of Poly (ADP-Ribose) Polymerase in Tumor Biopsies of Mouse Xenografts
Pharmacodynamic assay for evaluation of first-in-class pyruvate kinase-M2 activators in tumors.
Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors
PBMC PAR levels in healthy volunteers and patients with cancer after ex vivo ABT-888 treatment.
<p>(A) Pooled PBMCs from healthy volunteers were treated ex vivo for 2 h with increasing concentrations of ABT-888. PAR levels were then determined by PAR immunoassay and normalized (100%) to the vehicle-treated control. Error bars represent standard deviations from three separate experiments. PAR levels were compared between (B) PBMCs from four healthy volunteers (HV) and four patients (Pt) with cancer and (C) 40 individual healthy volunteers. PBMC samples were treated ex vivo with 0.21 µM ABT-888 (the target clinical exposure) for 2 h and PAR levels are reported relative to vehicle-treated controls (100%). Dashed line, 50% reduction.</p
PAR levels in PBMCs collected from patients during the Phase 0 clinical trial of ABT-888.
<p>Abbreviations: SD, standard deviation; CV, coefficient of variation; NV, no value; LLQ, PAR level below lower limit of quantitation.</p>a<p>PBMCs were isolated from whole blood collected 7, 6, and 5 days prior to drug administration and immediately before drug administration (day 1).</p
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