Publications
74 results found
Stavraka C, Pinato DJ, O'Cathail SM, et al., 2012, Multivariate screening of prognostic factors identifies a novel, simple and objective marker to optimize patient selection and predict survival benefit in early phase trials., 48th Annual Meeting of the American-Society-of-Clinical-Oncology, Publisher: J Clin Oncol
Pinato DJ, Stavraka C, O'Cathail SM, et al., 2012, Inflammation based scores can optimize the selection of patients with advanced cancer considered for early phase clinical trials., 48th Annual Meeting of the American-Society-of-Clinical-Oncology
Omlin A, Spicer J, Sarker D, et al., 2012, A pharmacokinetic (PK) pharmacodynamics (PD) driven first-in-human study of the oral class I PI3K inhibitor CH5132799, in patients with advanced solid tumours., 48th Annual Meeting of the American-Society-of-Clinical-Oncology
Soria J-C, Gan HK, Arkenau H-T, et al., 2012, Phase I clinical and pharmacologic study of the focal adhesion kinase (FAK) inhibitor GSK2256098 in pts with advanced solid tumors, 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Pinato DJ, Stavraka C, O'Cathail SM, et al., 2012, Use of inflammation-based scores to optimize the selection of patients with advanced cancer considered for early-phase clinical trials, 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Stavraka C, Ford A, Ghaem-Maghami S, et al., 2012, A study of symptoms described by ovarian cancer survivors, GYNECOLOGIC ONCOLOGY, Vol: 125, Pages: 59-64, ISSN: 0090-8258
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- Citations: 54
Syed N, 2012, Polo Like Kinase 2 Tumour Suppressor and cancer biomarker: new perspectives on drug sensitivity/resistance in ovarian cancer, Oncotarget, Vol: 3, Pages: 78-83, ISSN: 1949-2553
The polo-like kinase PLK2 has recently been identified as a potential theranostic marker in the management of chemotherapy sensitive cancers. The methylation status of the PLK2 CpG island varies with sensitivity to paclitaxel and platinum in ovarian cancer cell lines. Importantly, extrapolation of these in vitro data to the clinical setting confirms that the methylation status of the PLK2 CpG island predicts outcomes in patients treated with carboplatin & paclitaxel chemotherapy. A second cell cycle regulator, p57Kip2, is also subject to epigenetic silencing in carboplatin resistance in vitro and in vivo, emphasising that cell cycle regulators are important determinants of sensitivity to chemotherapeutic agents and providing insights into the phenomenon of collateral drug sensitivity in oncology. Understanding the mechanistic basis and identification of robust biomarkers to predict collateral sensitivity may inform optimal use of chemotherapy in patients receiving multiple lines of treatment.
Li HK, Harding V, Williamson R, et al., 2012, Cerebral Sinus Thrombosis and Leptomeningeal Carcinomatosis in a Patient With Ovarian Cancer, JOURNAL OF CLINICAL ONCOLOGY, Vol: 30, Pages: E19-E20, ISSN: 0732-183X
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- Citations: 8
Gabra H, Blagden S, 2012, Epithelial Ovarian Cancer, Pages: 760-775
Although relatively uncommon, epithelial ovarian cancer is the most lethal gynaecological malignancy, partly due to its insidious presentation but also because of its intrinsic histological and molecular heterogeneity. The 5-year survival rate has recently improved to almost 50%, predominantly through optimal specialist surgical intervention and the use of platinum-based chemotherapy. However, for the majority of patients, the disease will relapse following initial treatment and become increasingly chemotherapy resistant with each episode of recurrence. Future treatment strategies, as well as improving response to front-line therapy, are focusing on ways to overcome chemotherapy resistance in the relapsed setting, with the judicious use of novel cytotoxic and/or targeted therapies. These options become more feasible with improvements in our understanding of the molecular behaviour of the disease and of its various histological subtypes. We summarize the current status quo in the surgical and medical management of ovarian cancer and present results of a number of key studies that have explored genetically, molecularly and histologically targeted strategies in the treatment of this disease. © 2012 John Wiley and Sons, Ltd..
Sharma R, Graham J, Blagden S, et al., 2011, Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer, BMC Cancer, Vol: 11, ISSN: 1471-2407
BackgroundPlatinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored.MethodsWe treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel.ResultsWe were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity.ConclusionsWe conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.
Gungor H, Saleem A, Agarwal R, et al., 2011, Pharmacokinetic (PK)/pharmacodynamic (PD) analysis of escalating repeat doses of the AKT inhibitor GSK2141795 (GSK795) in patients (pts) with ovarian cancer., JOURNAL OF CLINICAL ONCOLOGY, Vol: 29, ISSN: 0732-183X
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- Citations: 7
Olmos D, Barker D, Sharma R, et al., 2011, Phase I Study of GSK461364, a Specific and Competitive Polo-like Kinase 1 Inhibitor, in Patients with Advanced Solid Malignancies, CLINICAL CANCER RESEARCH, Vol: 17, Pages: 3420-3430, ISSN: 1078-0432
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- Citations: 126
Syed N, Crook T, 2011, Polo-like kinase Plk2 is an epigenetic determinant of chemosensitivity and clinical outcomes in ovarian cancer, Cancer Research
Blagden SP, Willis AE, 2011, The biological and therapeutic relevance of mRNA translation in cancer, NATURE REVIEWS CLINICAL ONCOLOGY, Vol: 8, Pages: 280-291, ISSN: 1759-4774
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- Citations: 115
Agarwal R, Blagden S, 2011, Molecular targets in ovarian cancer, Cancer and Chemotherapy Reviews, Vol: 6, Pages: 37-44, ISSN: 1885-740X
Despite advances in the management of epithelial ovarian cancer, it remains the most lethal of gynecological malignancies in the UK. Ovarian cancer is a complex disease, both in its molecular and clinical behavior. Targeted therapies have yet to show an improvement in five-year survival when added to standard cytotoxic chemotherapy. However, a recent redefinition of the disease along with the discovery of unique molecular targets has provided new avenues for therapeutic development. In this review, we summarize the main targeted therapies that are currently in clinical development alongside those that are due to enter the clinical arena.
Burrows C, Latip NA, Lam S-J, et al., 2010, The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration, Nucleic Acids Research, Vol: 38, Pages: 5542-5553, ISSN: 0305-1048
The RNA binding protein Larp1 was originally shown to be involved in spermatogenesis, embryogenesis and cell-cycle progression in Drosophila. Our data show that mammalian Larp1 is found in a complex with poly A binding protein and eukaryote initiation factor 4E and is associated with 60S and 80S ribosomal subunits. A reduction in Larp1 expression by siRNA inhibits global protein synthesis rates and results in mitotic arrest and delayed cell migration. Consistent with these data we show that Larp1 protein is present at the leading edge of migrating cells and interacts directly with cytoskeletal components. Taken together, these data suggest a role for Larp1 in facilitating the synthesis of proteins required for cellular remodelling and migration.
Blagden SP, Gatt MK, Archambault V, et al., 2009, <i>Drosophila</i> Larp associates with poly(A)-binding protein and is required for male fertility and syncytial embryo development, DEVELOPMENTAL BIOLOGY, Vol: 334, Pages: 186-197, ISSN: 0012-1606
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- Citations: 67
Blagden S, Gabra H, 2009, Promising molecular targets in ovarian cancer, CURRENT OPINION IN ONCOLOGY, Vol: 21, Pages: 412-419, ISSN: 1040-8746
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- Citations: 19
Scott EN, Thomas AL, Molife LR, et al., 2009, A phase I dose escalation study of the pharmacokinetics and tolerability of ZK 304709, an oral multi-targeted growth inhibitor (MTGI<SUP>™</SUP>), in patients with advanced solid tumours, CANCER CHEMOTHERAPY AND PHARMACOLOGY, Vol: 64, Pages: 425-429, ISSN: 0344-5704
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- Citations: 25
Olmos D, Allred A, Sharma R, et al., 2009, Phase I first-in-human study of the polo-like kinase-1 selective inhibitor, GSK461364, in patients with advanced solid tumors, 45th Annual Meeting of the American-Society-of-Clinical-Oncology, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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- Citations: 11
Sharma R, Graham J, Mitchell H, et al., 2009, Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer, British Journal of Cancer, Vol: 100, Pages: 707-712, ISSN: 0007-0920
There is increasing evidence of the efficacy of dose-dense therapy in the management of platinum-resistant/refractory ovarian cancer. We report our experience of extended weekly carboplatin and paclitaxel in this population group. Twenty patients with platinum-resistant/refractory ovarian cancer received carboplatin AUC 3 and paclitaxel 70 mg m−2 on day 1, 8, 15 q 4 weekly for six planned cycles. Toxicity was assessed using Common Toxicity Criteria. Response was evaluated using radiological and CA125 criteria. Median age was 61 years (range 40–74 years). Median number of prior therapies is three (range 1–8). Response rate was 60% by radiological criteria (RECIST) and 76% by CA125 assessment. Grade 3 toxicities consisted of neutropenia (29% of patients) and anaemia (5%). One patient experienced grade 4 neutropenia. No grade 3/4 thombocytopaenia was reported. Fatigue, nausea and peripheral neuropathy were the most frequent non-hematological side effects. Median progression-free survival was 7.9 months and overall survival was 13.3 months. The dynamics of response to dose-dense therapy were as rapid as with front-line therapy within the same patient. This dose-dense regimen can be extended to at least 18 weekly cycles over 6 months and is well tolerated with high response rates in heavily pre-treated, platinum-resistant ovarian cancer. It forms a highly active and tolerable cytotoxic scaffold to which molecular-targeted therapies can be added in platinum-resistant ovarian cancer.
Blagden S, Olmos D, Sharma R, et al., 2008, A phase I first-in-human study of the polo-like kinase 1-selective inhibitor, GSK461364, in patients with advanced solid tumors, 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 135-136, ISSN: 1359-6349
Blagden S, Olmos D, Sharma R, et al., 2008, Characterization of BI 6727, a novel Polo-like kinase inhibitor with a distinct pharmacokinetic profile and efficacy in a model of taxane-resistant colon cancer, 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 135-135, ISSN: 1359-6349
Blagden S, Gabra H, 2008, Future directions in the management of epithelial ovarian cancer, FUTURE ONCOLOGY, Vol: 4, Pages: 403-411, ISSN: 1479-6694
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- Citations: 7
Tuthill MH, Borley J, Gabra H, et al., 2008, Patterns of relapse in patients treated with surgery followed by platinum based chemotherapy for advanced epithelial ovarian cancer, JOURNAL OF CLINICAL ONCOLOGY, Vol: 26, ISSN: 0732-183X
Blagden SP, Molife LR, Seebaran A, et al., 2008, A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours, BRITISH JOURNAL OF CANCER, Vol: 98, Pages: 894-899, ISSN: 0007-0920
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- Citations: 58
Attard G, Kitzen J, Blagden SP, et al., 2007, A phase lb study of pertuzumab, a recombinant humanised antibody to HER2, and docetaxel in patients with advanced solid tumours, BRITISH JOURNAL OF CANCER, Vol: 97, Pages: 1338-1343, ISSN: 0007-0920
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- Citations: 58
Yap TA, Molife LR, Blagden SP, et al., 2007, Targeting cell cycle kinases and kinesins in anticancer drug development, EXPERT OPINION ON DRUG DISCOVERY, Vol: 2, Pages: 539-560, ISSN: 1746-0441
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- Citations: 10
Greystoke A, Blagden S, Thomas AL, et al., 2006, A phase I study of intravenous TZT-1027 administered on day 1 and day 8 of a three-weekly cycle in combination with carboplatin given on day 1 alone in patients with advanced solid tumours, ANNALS OF ONCOLOGY, Vol: 17, Pages: 1313-1319, ISSN: 0923-7534
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- Citations: 22
Blagden S, Seebaran A, Molife R, et al., 2005, Phase I study of ispinesib (SB-715992) in combination with docetaxel in patients with advanced solid tumors., AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics, Publisher: AMER ASSOC CANCER RESEARCH, Pages: 9119S-9119S, ISSN: 1078-0432
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