Making the Most of What We Have
(January 25th, 2016) It is typically more economical to repurpose old possessions than to go out and buy new ones. As it turns out, this same principle may also apply to cancer treatments.
The Repurposing Drugs in Oncology (ReDO) Project, a partnership between GlobalCures in the US and the Anticancer Fund in Belgium, is hunting down widely available medications that may have hidden anti-cancer properties. In a recent review, the project presented data on the potential benefits of repurposing diclofenac, a well-known anti-inflammatory drug.
The ReDO Project hopes to identify strong candidates from existing literature, and to compile and amplify this data by producing accessible reviews. Their review on diclofenac outlines evidence of the drug’s potential, which the project hopes will encourage clinical investigation.
Diclofenac falls under a class of medications known as non-steroidal anti-inflammatory drugs, or NSAIDs. It boosts the immune system and inhibits angiogenesis, two properties that make it attractive as a cancer treatment. Because it has already been widely studied as an anti-inflammatory, its toxicity level in humans is well established. Using diclofenac in conjunction with radiation or chemotherapy may increase those treatments’ effectiveness. The drug could have therapeutic benefit by interfering with the body’s wound-healing response at the time of cancer surgery, for instance. The tumour removal process sets in motion a sequence of events, which could awaken any remaining cancer cells.
“If you’ve got micrometastases - in the lungs, for example - and you’ve had breast cancer surgery, your body releases these factors to deal with the wound. These factors are going to flood through the body and the micrometastases in the lungs can suddenly come to life,” says Pan Pantziarka, a scientist with the Anticancer Fund. The hope is to minimise systemic recurrence of tumours by administering diclofenac before an incision is made.
A retrospective study led by Patrice Forget at the Catholic University of Leuven looked at 720 breast cancer patients who underwent mastectomies. Half the patients were treated with diclofenac or ketorolac, a cousin of diclofenac, prior to incision. The researchers observed a marked decrease in tumour recurrence and increased overall survival. The Anticancer Fund is now supporting a randomised controlled trial of ketorolac by Patrice Forget to confirm the retrospective results.
According to Vikas P. Sukhatme, a professor of medicine at Harvard Medical School and a co-founder of GlobalCures, doctors are currently reluctant to prescribe diclofenac in an anticancer context due to the lack of a definitive phase-3 trial. The practice of prescribing a drug off-label exposes them to risks. The ReDO Project hopes to change this situation with a successful, randomised clinical trial.
Older, multi-targeted agents, such as diclofenac, are often thought of as “dirty drugs” compared with newer, single-targeted agents. Pantziarka sees this protean quality as a strength. “These drugs don’t do just one thing; they do lots of different things at the same time and those different things work together to attack different parts of a tumour’s support systems.”
Diclofenac and others “don’t have that sexy wow-factor that a brand-new molecule would have,” says Pantziarka. “They’re considered old hat.” If studies are successful, however, they could solidify these medications as potential anticancer therapies.
The reason to study these treatments seems clear: successful candidates would provide a tested alternative to the costly and time-consuming process of drug development. These medications could help patients suffering from cancer now, as opposed to several years in the future.
Unfortunately, there is little financial incentive to study such drugs, many of which are already available as generics. “We’re in a situation where it’s probably more expensive for a clinician to run a clinical trial using a cheap drug like diclofenac than it is to run a trial using one of the most expensive drugs to come out of a pharmaceutical company,” says Pantziarka.
The ReDO Project has written protocols and identified individuals willing to conduct the trials. Sukhatme hopes that crowdfunding will fill in the final and essential piece of the puzzle: money.
“We hope that these efforts raise awareness that there are exciting, untapped opportunities that could significantly impact cancer care in the very near future,” Sukhatme says. “At the end of the day, the public must either fund trials with these drugs or not benefit from their potential use.”