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Harrogate, United Kingdom

Yorkshire Cancer Research is a registered charity that funds research, principally in Yorkshire, into the causes and cures of cancer. They do this by fundraising in Yorkshire and providing awards to Yorkshire based academic institutions. Through publishing and sharing the results of this research with the world's scientific community, Yorkshire Cancer Research hopes to develop more effective treatments for cancer sufferers world-wide.Yorkshire Cancer Research raises its money in Yorkshire and spends it in Yorkshire at its five centres of excellence based at Bradford University, Hull University, Leeds University, Sheffield University and York University and their associated teaching hospitals.They are the most successful regional medical research charity in the UK and fund internationally recognised research which focuses on a variety of cancers including: breast cancer, bowel cancer, cervical cancer, non-Hodgkin Lymphoma, ovarian cancer, prostate cancer, skin cancer and genetics of cancers. Yorkshire Cancer Research is not a regional division of a national charity - they are an independent charity, based and operating in Yorkshire only.Yorkshire Cancer Research are members of the Association of Medical Research Charities and the National Cancer Research Institute Wikipedia.

Destruction of cancer cells by genetically modified viral and nonviral vectors has been the aim of many research programs. The ability to target cytotoxic gene therapies to the cells of interest is an essential prerequisite, and the treatment has always had the potential to provide better and more long-lasting therapy than existing chemotherapies. However, the potency of these infectious agents requires effective testing systems, in which hypotheses can be explored both in vitro and in vivo before the establishment of clinical trials in humans. The real prospect of off-target effects should be eliminated in the preclinical stage, if current prejudices against such therapies are to be overcome. In this review we have set out, using adenoviral vectors as a commonly used example, to discuss some of the key parameters required to develop more effective testing, and to critically assess the current cellular models for the development and testing of prostate cancer biotherapy. Only by developing models that more closely mirror human tissues will we be able to translate literature publications into clinical trials and hence into acceptable alternative treatments for the most commonly diagnosed cancer in humans. Source

Guise T.A.,Indiana University | Brufsky A.,University of Pittsburgh | Coleman R.E.,Yorkshire Cancer Research
Current Medical Research and Opinion

Bone is the preferred site of metastasis for breast cancer, and presence of skeletal lesions is associated with significant morbidity and poor prognosis. Skeletal-related effects such as pain, pathologic fractures, spinal compression, and hypercalcemia are frequent consequences of skeletal lesions of breast cancer that have debilitating effects on the patients' quality of life. In addition to direct cancer effects on the skeleton, therapies commonly used to treat patients with breast cancer such as chemotherapy and aromatase inhibitors (AI) result in cancer therapy-induced bone loss (CTIBL) which is associated with increased risk of skeletal complications such as fractures. Bisphosphonates are a class of antiresorptive drugs that are now firmly established as the cornerstone of the management of skeletal-related events due to breast cancer. Other novel bone-targeting agents such as the anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody denosumab are also showing promising activity in the treatment of bone metastasis secondary to breast cancer. Moreover, recent provocative evidence suggests that bisphosphonates might also exhibit antitumor activity via direct and indirect mechanisms. The goal of this review is to summarize the pathophysiology of osteolytic bone lesions secondary to breast cancer, provide clinical evidence of currently available bone-targeted drugs in the treatment of bone metastasis and CTIBL, and explore the antitumor activity of current bone-targeted agents in patients with breast cancer. © 2010 Informa UK Ltd. Source

Coleman R.,Yorkshire Cancer Research | Body J.J.,Free University of Colombia | Aapro M.,Multidisciplinary Oncology Institute | Hadji P.,University of Marburg | Herrstedt J.,University of Southern Denmark
Annals of Oncology

There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling. This endocrine disturbance results in accelerated bone loss and an increased risk of osteoporosis and fractures that can have a significant negative impact on the lives of the rapidly expanding number of long-term cancer survivors. Finally, the bone marrow micro-environment is also intimately involved in the metastatic processes required for cancer dissemination, and there are emerging data showing that, at least in some clinical situations, the use of bone-targeted treatments can reduce metastasis to bone and has potential impact on patient survival. © The Author 2014. Source

Hadji P.,University of Marburg | Coleman R.,Academic Unit of Clinical Oncology | Coleman R.,Yorkshire Cancer Research | Gnant M.,Medical University of Vienna
Critical Reviews in Oncology/Hematology

Patients with breast cancer face substantial challenges to bone health from bone metastases, as well as from chemotherapy and endocrine therapies that generally elicit disease control at the cost of increased bone turnover. Consequently, maintaining bone health is of critical importance for these patients. Recently reported results from BOLERO-2 showed significant clinical benefits with adding everolimus to exemestane therapy in postmenopausal women with estrogen-receptor-positive breast cancer recurring or progressing despite nonsteroidal aromatase inhibitor therapy. Moreover, exploratory analyses from BOLERO-2 showed that adding everolimus may have beneficial effects on bone turnover and progressive disease in bone in this patient population. These results are supported by preclinical studies in which mTOR inhibition was associated with decreased osteoclast survival and activity. Thus, everolimus therapy may be able to ameliorate the negative effects of estrogen suppression on bone health. This review discusses the effects of mTOR inhibition on bone health during endocrine therapy. © 2013 The Authors. Source

Barrett-Lee P.,Velindre Cancer Center | Casbard A.,University of Cardiff | Abraham J.,Velindre Cancer Center | Hood K.,University of Cardiff | And 7 more authors.
The Lancet Oncology

Background: Bisphosphonates are routinely used in the treatment of metastatic bone disease from breast cancer to reduce pain and bone destruction. Zoledronic acid given by intravenous infusion has been widely used, but places a substantial logistical burden on both patient and hospital. As a result, the use of oral ibandronic acid has increased, despite the absence of comparative data. In the ZICE trial, we compared oral ibandronic acid with intravenous zoledronic acid for the treatment of metastatic breast cancer to bone. Methods: This phase 3, open-label, parallel group active-controlled, multicentre, randomised, non-inferiority phase 3 study was done in 99 UK hospitals. Eligibility criteria included at least one radiologically confirmed bone metastasis from a histologically confirmed breast cancer. Patients with ECOG performance status 0 to 2 and clinical decision to treat with bisphosphonates within 3 months of randomisation were randomly assigned to receive 96 weeks of treatment with either intravenous zoledronic acid at 4 mg every 3-4 weeks or oral ibandronic acid 50 mg daily. Randomisation (1:1) was done via a central computerised system within stratified block sizes of four. Randomisation was stratified on whether patients had current or planned treatment with chemotherapy; current or planned treatment with hormone therapy; and whether they had a previous skeletal-related event within the last 3 months or had planned radiotherapy treatment to the bone or planned orthopaedic surgery due to bone metastases. The primary non-inferiority endpoint was the frequency and timing of skeletal-related events over 96 weeks, analysed using a per-protocol analysis. All active (non-withdrawn) patients have now reached the 96-week timepoint and the trial is now in long-term follow-up. The trial is registered with ClinicalTrials.gov, number NCT00326820. Findings: Between Jan 13, 2006, and Oct 4, 2010, 705 patients were randomly assigned to receive ibandronic acid and 699 to receive zoledronic acid; three patients withdrew immediately after randomisation. The per-protocol analysis included 654 patients in the ibandronic acid group and 672 in the zoledronic acid group. Annual rates of skeletal-related events were 0·499 (95% CI 0·454-0·549) with ibandronic acid and 0·435 (0·393-0·480) with zoledronic acid; the rate ratio for skeletal-related events was 1·148 (95% CI 0·967-1·362). The upper CI was greater than the margin of non-inferiority of 1·08; therefore, we could not reject the null hypothesis that ibandronic acid was inferior to zoledronic acid. More patients in the zoledronic acid group had renal toxic effects than in the ibandronic acid group (226 [32%] of 697 vs 172 [24%] of 704) but rates of osteonecrosis of the jaw were low in both groups (nine [1%] of 697 vs five [<1%] of 704). The most common grade 3 or 4 adverse events were fatigue (97 [14%] of 697 patients allocated zoledronic acid vs 98 [14%] of 704 allocated ibandronic acid), increased bone pain (92 [13%] vs 86 [12%]), joint pain (42 [6%] vs 38 [5%]), infection (33 [5%] vs 24 [3%]), and nausea or vomiting (38 [5%] vs 41 [6%]). Interpretation: Our results suggest that zoledronic acid is preferable to ibandronic acid in preventing skeletal-related events caused by bone metastases. However, both drugs have acceptable side-effect profiles and the oral formulation is more convenient, and could still be considered if the patient has a strong preference or if difficulties occur with intravenous infusions. Funding: Roche Products Ltd (educational grant), supported by National Institute for Health Research Cancer Network, following endorsement by Cancer Research UK (CRUKE/04/022). © 2014 Elsevier Ltd. Source

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