MedicalResearch.com Interview with:
Dr Pan Pantziarka, PhD
Program Director, Drug Repurposing: Anticancer Fund
Coordinator: Repurposing Drugs in Oncology
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Repurposing Drugs in Oncology (ReDO) project is an on-going collaboration assessing the evidence of anticancer activity in a wide range of already licensed non-cancer drugs. A subset of these drugs have a sufficient level of evidence to support clinical investigation and these are profiled in detail in order to synthesise the existing evidence and to bring it to the attention of clinical researchers.
In the case of the PDE5 inhibitors sildenafil, tadalafil and vardenafil the evidence is clear that these drugs have multiple anticancer mechanisms of action at clinically relevant dosing. In particular there is evidence that these drugs target anti-tumour immune responses, as shown from a small number of early stage clinical trials. This opens up the prospect of using these cheap and widely available drugs in combination with existing therapies to improve the number and duration of responses. The chance to increase the therapeutic effectiveness of immune checkpoint inhibitors is especially compelling and definitely warrants clinical research.
Response: What recommendations do you have for future research as a result of this work?
Response: Our first recommendation is further clinical research, particularly in some hard to treat cancers such as glioblastoma multiforme (GBM). As with the other ReDO drugs, we do not expect PDE5 inhibitors to act as monotherapies but to enhance the response to existing treatments. In the case of GBM these drugs can alter blood-brain-barrier permeability and therefore increase the range of drugs which may be used to treat brain tumours. For a disease like GBM, which has few effective treatment options, the chance to try new treatment options by adding PDE5 inhibitors is certainly worthy of investigation. Similarly improving the response of standard anti-cancer drugs by improving the existing immune response offers a potential path to clinically meaningful benefits.
MedicalResearch.com: What should readers take away from your report?
Response: This paper yet again highlights the potential of existing drugs to target important cancer-specific pathways. We should view the existing range of licensed non-cancer drugs as a reservoir of therapeutic molecules that we can draw on as our understanding of the molecular drivers of cancer. For example, we now know that many tumours over-express beta-adrenergic receptors and that targeting these with beta-blockers such as propranolol may decrease proliferation and multiple metastatic pathways. Similarly there is growing evidence that many tumour types over-express PDE5, therefore blocking this with sildenafil or tadalafil will have direct benefits. Yet far too many precision oncology projects ignore non-cancer drugs and thereby limit potentially druggable targets.
Repurposing drugs in oncology (ReDO)—selective PDE5 inhibitors as anti-cancer agents
Pan Pantziarka1,2, Vidula Sukhatme3, Sergio Crispino1, Gauthier Bouche1, Lydie Meheus1 and Vikas P Sukhatme3,4
ecancer 12 824 / https://doi.org/10.3332/ecancer.2018.824
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