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Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.
Olaparib has few of the adverse effects of conventional chemotherapy, inhibits PARP, and has antitumor activity in cancer associated with the BRCA1 or BRCa2 mutation.
Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval.
  • P. Fong, T. Yap, S. Kaye
  • Biology, Medicine
    Journal of clinical oncology : official journal…
  • 20 May 2010
Olaparib has antitumor activity in BRCA1/2 mutation ovarian cancer, which is associated with platinum sensitivity, a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory subgroups.
Phase I Dose-Escalation Study of the Pan-HER Inhibitor, PF299804, in Patients with Advanced Malignant Solid Tumors
Both continuous and intermittent treatment schedules were well tolerated, and encouraging signs of antitumor activity were observed in gefitinib/erlotinib treated NSCLC patients.
A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours
E7080 is well tolerated at doses up to 25 mg per day and has dose-linear kinetics with no drug accumulation after 4 weeks’ administration, and encouraging anti-tumour efficacy was observed in patients with melanoma and renal cell carcinoma.
Clinical experience with aurora kinase inhibitors: a review.
The most recent advances in the development of aurora kinase inhibitors are summarized, with a focus on the clinical data.
Clinical evaluation of AZD1152, an i.v. inhibitor of Aurora B kinase, in patients with solid malignant tumors.
AZD1152 was generally well tolerated with neutropenia being the most frequently reported AE and DLT and no objective tumor responses were observed at any dose or schedule, although stable disease, as defined by RECIST, was achieved in 15 patients overall.
AZD2281 (KU-0059436), a PARP (poly ADP-ribose polymerase) inhibitor with single agent anticancer activity in patients with BRCA deficient ovarian cancer: Results from a phase I study
A first-in-human Phase I trial of AZD2281, a novel, potent orally active PARP inhibitor, in BRCA-deficient ovarian cancer, with dose escalation guided by toxicity, pharmacokinetic and pharmacodynamic data, finding that the maximum tolerated dose was 400mg bd.
Preliminary activity and safety results from a phase I clinical trial of PF-00299804, an irreversible pan-HER inhibitor, in patients (pts) with NSCLC
Results in pts with refractory NSCLC enriched for HER gene amplification, HER1/HER2 mutation, or wild type (WT) KRAS, within the phase I study are reported.
First in human phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of KU-0059436 (Ku), a small molecule inhibitor of poly ADP-ribose polymerase (PARP) in cancer patients (p), including
3529 Background: Ku is a novel, potent, orally active PARP-1 and 2 inhibitor. It induces selective cytotoxicity in cells with defective homologous recombination repair such as BRCA1/2 deficient tumor