The class of drugs currently prescribed to treat male erectile dysfunction has been flagged for its potential to be included in new trials for anti-cancer drugs, in a new clinical study published today in the open access journal, ecancermedicalscience.
The paper is the latest publication from the Repurposing Drugs in Oncology (ReDO) project, an international collaboration between the Anticancer Fund, Belgium, and USA-based GlobalCures.
With the high cost of new cancer drugs a huge political issue faced by governments across the world, the mission of the Anticancer Fund is to identify which commonly (and cheaply) available existing drugs have untapped life-saving potential.
In their paper, the researchers have identified that selective phosphodiesterase 5 (PDE5) inhibitors have the potential to be used in new drug trials. These PDE5 inhibitors are a class of drugs that include sildenafil, tadalafil and vardenafil (more commonly known by their brand names Viagra ®, Cialis ® and Levitra®).
"In many respects sildenafil is the ultimate repurposing success story," says Dr Pan Pantziarka of the Anticancer Fund. "It was originally developed for angina, repurposed for erectile dysfunction and then again for pulmonary arterial hypertension, and now it has the potential to be repurposed again as an anti-cancer drug."
Like many of the other drugs that the Repurposing Drugs in Oncology (ReDO) Project has profiled in publications in ecancermedicalscience, PDE5 inhibitors show a wide range of mechanisms of action in different cancer types, such as glioblastoma multiforme - a rare disease where clinically meaningful advances are desperately needed.
"Checkpoint inhibitors have radically altered the landscape in oncology, but there remain significant challenges in terms of increasing the number and duration of responses," Pantziarka explains.
"Emerging evidence, summarised in this paper, suggests that PDE5 inhibitors may be one mechanism for achieving this."
"It would be ironic if the key to improving outcomes from some of the most expensive drugs in oncology comes from repurposing some of the cheapest non-oncology drugs."
The paper also explores the issue that finding new agents able to cross the blood-brain-barrier is a challenge which severely limits the range of drugs available to treat brain tumours. There is some evidence that drugs not currently licenced for cancer treatment like the PDE5 inhibitors, are able to increase permeability so that drug delivery to brain tumours is improved - thereby potentially opening the door to new therapeutic options for patients.
The paper includes a broad range of data, pre-clinical and clinical, has been summarised and presented to make the case that these commercially available and widely used PDE5 inhibitors are very strong candidates for repurposing as anticancer agents.
These low-cost, low-toxicity drugs show potential to be included with current and emerging standard of care treatments in oncology.
The researchers' hope is that this paper will bring the potential of this class of drugs to the attention of more clinicians and researchers engaged in clinical trials. A number of small, early phase trials are on-going, but the ReDO group believe that it is time for much larger efficacy trials to begin, so that the promise of these cheap repurposed medications can be fully realised.
Previous papers from the ReDO project have explored how inexpensive, common drugs such as beta-blockers and anti-fungal remedies can be "repurposed" and used as part of cancer treatments.
This paper was authored by Pan Pantziarka, Vidula Sukhatme, Sergio Crispino, Gauthier Bouche, Lydie Meheus and Vikas P Sukhatme.
Pan Pantziarka is available for comment.
Citation information and links
Pantziarka Pan, Sukhatme Vidula, Crispino Sergio, Bouche Gauthier, Meheus Lydie and Sukhatme Vikas P (2018) Repurposing drugs in oncology (ReDO)--selective PDE5 inhibitors as anti-cancer agents ecancer 12 824
About ecancermedicalscience (ecancer.org)
ecancermedicalscience (ecancer) is the official open access journal of the Organisation of European Cancer Institutes (OECI) and the European Institute of Oncology (IEO), Milan.
The journal was established in 2007 by Professor Umberto Veronesi and Professor Gordon McVie with the mission to break down the financial barriers to accessing cancer research and education.
The journal is not for profit and only charges authors an article publication fee if they have specific funding for publishing. So far over 2000 authors have published for free. The journal is funded by the Swiss based ECMS foundation, educational grants, sponsorship and charitable donations.