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Brussels, Belgium

Bouche G.,Anticancer Fund | Andre N.,Metronomics Global Health Initiative | Andre N.,Aix - Marseille University | Banavali S.,Tata Memorial Center | And 23 more authors.

The Fourth Metronomic and Anti-angiogenic Therapy Meeting was held in Milan 24-25 June 2014. The meeting was a true translational meeting where researchers and clinicians shared their results, experiences, and insights in order to continue gathering useful evidence on metronomic approaches. Several speakers emphasised that exact mechanisms of action, best timing, and optimal dosage are still not well understood and that the field would learn a lot from ancillary studies performed during the clinical trials of metronomic chemotherapies. From the pre-clinical side, new research findings indicate additional possible mechanisms of actions of metronomic schedule on the immune and blood vessel compartments of the tumour micro-environment. New clinical results of metronomic chemotherapy were presented in particular in paediatric cancers [especially neuroblastoma and central nervous system (CNS) tumours], in angiosarcoma (together with beta-blockers), in hepatocellular carcinoma, in prostate cancer, and in breast cancer. The use of repurposed drugs such as metformin, celecoxib, or valproic acid in the metronomic regimen was reported and highlighted the potential of other candidate drugs to be repurposed. The clinical experiences from low- and middle-income countries with affordable regimens gave very encouraging results which will allow more patients to be effectively treated in economies where new drugs are not accessible. Looking at the impact of metronomic approaches that have been shown to be effective, it was admitted that those approaches were rarely used in clinical practice, in part because of the absence of commercial interest for companies. However, performing well-designed clinical trials of metronomic and repurposing approaches demonstrating substantial improvement, especially in populations with the greatest unmet needs, may be an easier solution than addressing the financial issue. Metronomics should always be seen as a chance to come up with new innovative affordable approaches and not as a cheap rescue strategy. © the authors; licensee ecancermedicalscience. Source

Bertolini F.,Italian National Cancer Institute | Sukhatme V.P.,Beth Israel Deaconess Medical Center | Bouche G.,Anticancer Fund
Nature Reviews Clinical Oncology

In most countries, healthcare service budgets are not likely to support the current explosion in the cost of new oncology drugs. Repurposing the large arsenal of approved, non-anticancer drugs is an attractive strategy to offer more-effective options to patients with cancer, and has the substantial advantages of cheaper, faster and safer preclinical and clinical validation protocols. The potential benefits are so relevant that funding of academically and/or independently driven preclinical and clinical research programmes should be considered at both national and international levels. To date, successes in oncology drug repurposing have been limited, despite strong evidence supporting the use of many different drugs. A lack of financial incentives for drug developers and limited drug development experience within the non-profit sector are key reasons for this lack of success. We discuss these issues and offer solutions to finally seize this opportunity in the interest of patients and societies, globally. © 2015 Macmillan Publishers Limited. Source

Pantziarka P.,Anticancer Fund | Bouche G.,Anticancer Fund | Meheus L.,Anticancer Fund | Sukhatme V.,GlobalCures Inc. | And 2 more authors.

The Repurposing Drugs in Oncology (ReDO) Project seeks to repurpose well-known and well-characterised non-cancer drugs for new uses in oncology. The rationale for this project is presented, examining current issues in oncological drug development, challenges for health systems, and existing and future patient needs. In addition to discussing the advantages of repurposing, the paper also outlines some of the characteristics used in the selection of drug candidates by this project. Challenges in moving candidate drugs into clinical trial and subsequent practice are also discussed. © the authors; licensee ecancermedicalscience. Source

Van Nuffel A.M.T.,Anticancer Fund | Sukhatme V.,GlobalCures Inc. | Pantziarka P.,Anticancer Fund | Meheus L.,Anticancer Fund | And 3 more authors.

Clarithromycin (CAM) is a well-known macrolide antibiotic available as a generic drug. CAM is traditionally used for many types of bacterial infections, treatment of Lyme disease and eradication of gastric infection with Helicobacter pylori. Extensive preclinical and clinical data demonstrate a potential role for CAM to treat various tumours in combination with conventional treatment. The mechanisms of action underlying the anti-tumour activity of CAM are multiple and include prolonged reduction of pro-inflammatory cytokines, autophagy inhibition, and anti-angiogenesis. Here, we present an overview of the current preclinical (in vitro and in vivo) and clinical evidence supporting the role of CAM in cancer. Overall these findings justify further research with CAM in many tumour types, with multiple myeloma, lymphoma, chronic myeloid leukaemia (CML), and lung cancer having the highest level of evidence. Finally, a series of proposals are being made to further investigate the use of CAM in clinical trials which offer the greatest prospect of clinical benefit to patients. © the authors. Source

Pantziarka P.,Anticancer Fund | Bouche G.,Anticancer Fund | Meheus L.,Anticancer Fund | Sukhatme V.,GlobalCures Inc. | And 2 more authors.

Cimetidine, the first H2 receptor antagonist in widespread clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical and clinical studies for a number of different cancer types. These data are summarised and discussed in relation to a number of distinct mechanisms of action. Based on the evidence presented, it is proposed that cimetidine would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of cimetidine as an anti-cancer therapeutic is warranted. Furthermore, there is compelling evidence that cimetidine administration during the peri-operative period may provide a survival benefit in some cancers. A number of possible combinations with other drugs are discussed in the supplementary material accompanying this paper. Copyright: © the authors; licensee ecancermedicalscience. Source

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