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-- Cures Within Reach (CWR) is excited to announce the launch of Cures Within Reach for Cancer (CWR-4C), a Boston-based initiative that aims to fund and facilitate the development of new cancer treatments based on repurposing of generic drugs previously approved by the Food and Drug Administration for other indications."Repurposed generics offer a unique opportunity for inexpensive, safe, and highly effective cancer treatments that could be developed in half the time of new drugs, but they are being overlooked by drug developers due to a lack of financial incentives typically provided by patent protection or other financial exclusivity,"said CWR-4C's Executive Director Dr. Laura Kleiman. "This is a huge loss for cancer patients who could benefit from these new therapies, and a missed opportunity to decrease the cost of cancer care."Dozens of these very promising cancer treatments are not being fully developed because they do not fit the standard drug development model where drugs must be highly profitable for pharmaceutical companies. Organizations such as GlobalCures and the Anticancer Fund have spent years identifying these repurposing opportunities by examining published data from thousands of pre-clinical studies and Phase I/II clinical trials. These groups have published a series of articles describing the data and rationale for some of the most promising candidates as part of the Repurposing Drugs in Oncology Project.CWR-4C will raise funds to create a drug repurposing KnowledgeBase. The KnowledgeBase will curate the large amount of published information and systematically assess and prioritize repurposing opportunities for further development. The KnowledgeBase will be made available to physicians, patients, and researchers to increase awareness of the existing data."Many of the most promising candidates can go straight into definitive Phase II/III clinical trials, without additional pre-clinical or Phase I studies," said CWR-4C's Director of Strategic Development Dr. Dale Flanders. "We will identify funding and develop new incentives to enable these trials. For instance, pre-surgical use of the NSAID ketorolac could immediately be evaluated in Phase III trials for early-stage lung and breast cancers. The rationale for this inexpensive treatment is strongly supported by clinical data. By preventing cancer recurrence, it could save more than 15,000 lives and $1.5 billion in healthcare costs each year in the U.S. alone."CWR-4C will explore various funding mechanisms for generic drug repurposing, including purely philanthropic and innovative sustainability models, and work with government to create new incentives. CWR has been assessing the use of social impact bonds to fund repurposing research and leverage the billions of dollars of healthcare savings that effective repurposed therapies could generate. CWR-4C plans to extend this effort for large cancer clinical trials.Even with positive outcomes from Phase III trials, repurposed generics may not become part of standard medical care. The CWR-4C team believes that this is because they are not developed by industry, and therefore suffer from limited financial resources, barriers to acceptance, and lack of a dedicated advocate. CWR-4C will fill this role to help change standard of care and insurance reimbursement so all cancer patients can access and benefit from these valuable treatments.Dr. Bruce Bloom, President and Chief Science Officer of CWR, explains why CWR-4C is critical to creating patient impact through drug repurposing. "Cures Within Reach for Cancer will work on both the global and individual levels. In addition to being the driver for making repurposed drugs widely available following successful clinical trials, Cures Within Reach for Cancer will help cancer patients now. There is a wealth of scientific and clinical data that can guide creation of treatment protocols for cancer patients who do not have effective therapies, but it is difficult for physicians to find and assess the treatment options. Cures Within Reach for Cancer's KnowledgeBase will facilitate this process so physicians and patients can make well-informed decisions about off-label use.""Cures Within Reach has a long track record of funding Phase I/II clinical trials for repurposed drugs and changing standard of care for rare diseases," said Dr. Kleiman. "We are thrilled to partner with Bruce and his team to increase funding for and accelerate development of very promising cancer treatments."ABOUT CURES WITHIN REACHCures Within Reach works to catalyze repurposing research for all diseases to quickly and affordably improve patient lives. This is accomplished through collaborations that connect researchers and funding, by facilitating crowdsourcing and community, and by identifying alternative financing models and incentives. More information at http://www.cureswithinreach.org ABOUT CURES WITHIN REACH FOR CANCERCures Within Reach for Cancer aims to 1) systematically assess and prioritize generic drug repurposing opportunities through the creation of a KnowledgeBase;2) develop a sustainable model to fund Phase II/III clinical trials and facilitate the studies; and 3) advocate for the treatments to be incorporated into standard of care so all cancer patients can access and benefit from these new and affordable therapies. More information at http://www.cureswithinreach.org/ cancer


Bertolini F.,Italian National Cancer Institute | Sukhatme V.P.,Beth Israel Deaconess Medical Center | Bouche G.,Anticancer Fund
Nature Reviews Clinical Oncology | Year: 2015

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.


PubMed | Anticancer Fund, Beth Israel Deaconess Medical Center and Italian National Cancer Institute
Type: Journal Article | Journal: Nature reviews. Clinical oncology | Year: 2015

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.


PubMed | Massachusetts General Hospital, Dana-Farber Cancer Institute, Italian National Cancer Institute, Boston University and 12 more.
Type: | Journal: Ecancermedicalscience | Year: 2016

The 5


Pantziarka P.,Anticancer Fund | Bouche G.,Anticancer Fund | Meheus L.,Anticancer Fund | Sukhatme V.,GlobalCures Inc. | And 2 more authors.
ecancermedicalscience | Year: 2014

Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical studies across a number of different cancer types. Significantly, there are also two case reports of anti-cancer activity in humans. The data are summarised and discussed in relation to suggested mechanisms of action. Based on the evidence presented, it is proposed that mebendazole would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of mebendazole as an anti-cancer therapeutic is warranted. A number of possible combinations with other drugs are discussed in the Appendix. Copyright: © the authors; licensee ecancermedicalscience.


PubMed | Anticancer Fund, Beth Israel Deaconess Medical Center and GlobalCures Inc
Type: | Journal: Ecancermedicalscience | Year: 2015

Nitroglycerin (NTG), a drug that has been in clinical use for more than a century, has a range of actions which make it of particular interest in an oncological setting. It is generally accepted that the main mechanism of action of NTG is via the production of nitric oxide (NO), which improves cardiac oxygenation via multiple mechanisms including improved blood flow (vasodilation), decreased platelet aggregation, increased erythrocyte O2 release and decreased mitochondrial utilization of oxygen. Its vasoactive properties mean that it has the potential to exploit more fully the enhanced permeability and retention effect in delivering anti-cancer drugs to tumour tissues. Moreover NTG can reduce HIF-1 levels in hypoxic tumour tissues and this may have anti-angiogenic, pro-apoptotic and anti-efflux effects. Additionally NTG may enhance anti-tumour immunity. Pre-clinical and clinical data on these anti-cancer properties of NTG are summarised and discussed. While there is evidence of a positive action as a monotherapy in prostate cancer, there are mixed results in NSCLC where initially positive results have yet to be fully replicated. Based on the evidence presented, a case is made that further exploration of the clinical benefits that may accrue to cancer patients is warranted. Additionally, it is proposed that NTG may synergise with a number of other drugs, including other repurposed drugs, and these are discussed in the supplementary material appended to this paper.


PubMed | Anticancer Fund, Beth Israel Deaconess Medical Center and GlobalCures Inc
Type: | Journal: Ecancermedicalscience | Year: 2015

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.


PubMed | Anticancer Fund, Beth Israel Deaconess Medical Center, GlobalCures Inc and Vrije Universiteit Brussel
Type: | Journal: Ecancermedicalscience | Year: 2016

Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers.


PubMed | Anticancer Fund, Beth Israel Deaconess Medical Center and GlobalCures
Type: | Journal: Ecancermedicalscience | Year: 2016

Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper.


PubMed | St George's, University of London and Anticancer Fund
Type: | Journal: Ecancermedicalscience | Year: 2015

Artesunate, a semi-synthetic and water-soluble artemisinin-derivative used as an anti-malarial agent, has attracted the attention of cancer researchers due to a broad range of anti-cancer activity including anti-angiogenic, immunomodulatory and treatment-sensitisation effects. In addition to pre-clinical evidence in a range of cancers, a recently completed randomised blinded trial in colorectal cancer has provided a positive signal for further clinical investigation. Used perioperatively artesunate appears to reduce the rate of disease recurrence - and the Neo-Art trial, a larger Phase II RCT, is seeking to confirm this positive effect. However, artesunate is a generic medication, and as with other trials of repurposed drugs, the Neo-Art trial does not have commercial sponsorship. In an innovative move, the trial is seeking funds directly from members of the public via a crowd-funding strategy that may have resonance beyond this single trial.

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