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Article
Open AccessiRFP (near-infrared fluorescent protein) imaging of subcutaneous and deep tissue tumours in mice highlights differences between imaging platforms
In vivo imaging using fluorescence is used in cancer biology for the detection, measurement and monitoring of tumours. This can be achieved with the expression of fluorescent proteins such as iRFP, which emits...
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Article
AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer – results of two parallel first-in-human phase I studies
Background AZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD). Methods In stu...
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Article
Open AccessA study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity
Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise resul...
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Article
Open AccessThe interaction between prognostic and pharmacodynamic biomarkers
Interactions between prognostic and pharmacodynamic (PD) biomarkers have received little attention.
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Article
Sustained tumour eradication after induced caspase-3 activation and synchronous tumour apoptosis requires an intact host immune response
Effective anticancer treatments often result in the induction of large amounts of tumour cell death. In vivo, such dying tumour cells are a potential source of antigens for T-cell stimulation. Although apoptosis ...
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Open AccessA caspase-3 ‘death-switch’ in colorectal cancer cells for induced and synchronous tumor apoptosis in vitro and in vivo facilitates the development of minimally invasive cell death biomarkers
Novel anticancer drugs targeting key apoptosis regulators have been developed and are undergoing clinical trials. Pharmacodynamic biomarkers to define the optimum dose of drug that provokes tumor apoptosis are...
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Article
Open AccessNeuroendocrine and epithelial phenotypes in small-cell lung cancer: implications for metastasis and survival in patients
Small-cell lung cancer (SCLC) has a very aggressive clinical course with early metastasis. This study investigated how the distinctive neuroendocrine characteristics contribute to disease progression and invas...
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Article
Open AccessMulti-level evidence that circulating CK18 is a biomarker of tumour burden in colorectal cancer
Circulating total cytokeratin 18 (tCK18) and/or caspase cleaved cytokeratin 18 (cCK18) (measured by M65 and M30 enzyme-linked immunosorbent assays (ELISAs), respectively) are used as pharmacodynamic (PD) bioma...
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Article
Open AccessEvaluation of cell death mechanisms induced by the vascular disrupting agent O**4503 during a phase I clinical trial
O**4503 is a tubulin-binding vascular disrupting agent that has recently completed a Cancer Research UK-sponsored phase I trial. Preclinical studies demonstrated early drug-induced apoptosis in tumour endothel...
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Article
Open AccessA pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker
Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet n...
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Article
Open AccessAssessment of circulating biomarkers for potential pharmacodynamic utility in patients with lymphoma
Treatment efficacy and toxicity are difficult to predict in lymphoma patients. In this study, the utility of circulating biomarkers in predicting and/or monitoring treatment efficacy/toxicity were investigated.
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Article
Open AccessCurrent status and future potential of somatic mutation testing from circulating free DNA in patients with solid tumours
Genetic alterations can determine the natural history of cancer and its treatment response. With further advances in DNA sequencing technology, multiple novel genetic alterations will be discovered which could...
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Article
Open AccessFit-for-purpose biomarker method validation for application in clinical trials of anticancer drugs
Clinical development of new anticancer drugs can be compromised by a lack of qualified biomarkers. An indispensable component to successful biomarker qualification is assay validation, which is also a regulato...
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Open AccessIssues on fit-for-purpose validation of a panel of ELISAs for application as biomarkers in clinical trials of anti-Angiogenic drugs
Successful introduction of new anticancer agents into the clinic is often hampered by a lack of qualified biomarkers. Studies have been conducted of 17 ELISAs representing a potential panel of pharmacodynamic/...
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Article
Open AccessConsiderations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer
Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or pred...
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Article
Open AccessA small molecule inhibitor of XIAP induces apoptosis and synergises with vinorelbine and cisplatin in NSCLC
Evasion of apoptosis contributes to the pathogenesis of solid tumours including non-small cell lung cancer (NSCLC). Malignant cells resist apoptosis through over-expression of inhibitor of apoptosis proteins (...
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Article
Open AccessBiomarkers of angiogenesis and their role in the development of VEGF inhibitors
Vascular endothelial growth factor (VEGF) has been confirmed as an important therapeutic target in randomised clinical trials in multiple disease settings. However, the extent to which individual patients bene...
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Article
Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death
Cells exposed to low-oxygen conditions (hypoxia) alter their metabolism to survive. This response, although vital during development and high-altitude survival, is now known to be a major factor in the selecti...
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Article
Open AccessDetection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study
This study investigated the potential clinical utility of circulating free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into a phase II study of AZD6244, a specific MEK1/2 inhibitor, in...
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Article
Open AccessContribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells
Hypoxia is as an indicator of poor treatment outcome. Consistently, hypoxic HCT116 colorectal cancer cells are resistant to oxaliplatin, although the mechanistic basis is unclear. This study sought to investig...
