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With the approval of sildenafil (Viagra), in the 1990s, in the treatment of erectile dysfunction an enzyme became popular, the [5] (19459003) phosphodiesterase type 5 (PDE5) . Later, it was discovered that selective inhibition of this enzyme could also be exploited in other areas such as pulmonary arterial hypertension and Raynaud's syndrome . Now, we discover that these drugs can also be useful in oncology. For example, if badociated with immunomodulators drugs now in vogue in cancer therapies, increase their immunomodulatory activity while if badociated with cardiotoxic chemotherapy as doxorubicin, reduces cardiotoxicity.
Because of their ability to overcome the blood-brain barrier, they can be applied in glioblastoma, as therapeutic enhancer of anticancer drugs
Repurposing on oncology
By doing a quick search (PDE5 inhibitors and cancer) on the engine of PubMed research come out of many books published in recent months. This confirms recent clinical evidence, in the oncological field, of selective cGMP phosphodiesterase type 5 (PDE-5) inhibitors, particularly sildenafil (Viagra), vardenafil ( Levitra) tadalafil (Cialis ). Few, however, with the last approved of the series, avanafil ( Spedra ).
This is a repositioning on their first indication, erectile dysfunction and the second indication, Pulmonary Arterial Hypertension .
This is a description of a work published in eCancerMedicalScience entitled "Reuse of Medicines in Oncology (ReDO) – selective PDE5 inhibitors as anticancer agents", first signature Pan Pantziarka . 19659010] This work reviews the three main PDE5 inhibitors and their clinical indications. It all began in the 1980s, with Pfizer research on the use of one of these inhibitors, sildenafil, in angina pectoris. The clinical study began in 1991. The unexpected side effects observed in patients males enrolled in the study, convinced Pfizer of the disease. study this product in erectile dysfunction. The clinical study began in 1993, reaching its approval in 1998 in the United States (FDA) and Europe (EMA).
In these 20-year-old sildenafil it has also been approved for use in pulmonary arterial hypertension and other indications, such as Raynaud's syndrome (or phenomenon) a rare disease affecting the arteries, characterized by a short vasospasm, or narrowing of blood vessels at the fingertips, hands or feet, which turn white or bluish
Tadalafil also found 39, other applications such as pulmonary arterial hypertension and benign prostatic hypertrophy . Little is described on the latest approved PDE5 inhibitor, avanafil ( Spedra ), as well as udenafil (Zydena) approved by EMA in the treatment of conbad cardiomyopathy . the function of the single ventricle while for the treatment of erectile dysfunction is only available in Russia, South Korea, the Philippines and Malaysia.
PDE5 in tumors
The researchers who pointed out the relationship are also Italian between phosphodestierases and cancer. A work of the University of Calabria, published in November last year on Oncotarget, first signature Ines Barone describes this report in detail. And a few months earlier, still on Oncotarget, another Italian research, with the participation of researchers from the University of Rome Tor Vergata, first signing Valeriana Cesarini reports the PDE5 with aggression from glioblastoma multiforme. We had already talked about how Viagra, as well as other drugs of the same clbad, should no longer be considered as drugs only useful in badual dysfunctions, but as useful tools in various fields
The development of these drugs for other applications lies in the patent aspects . Indeed, after patent expiry, these selective PDE5 inhibitors are widely available as " generic or equivalent ". Some efforts have been made to propose more modern formulations [VIDEO] but the fact remains that they are still available at low prices. For a company to make huge investments, for clinical studies, without the protection of a patent, there is the risk of losing investment . This is the real limit to the further development of these drugs. As long as the rules do not change, there will be few companies that will invest in this direction and, as we see, for the moment these are mainly academic research.
This article has been verified with:
- https://www.aboutpharma.com/blog/2018/06/25/la-terza-vita-del-viagra-un-possibile-antitumoral/
- https://ecancer.org/journal/ 12 / full / 824-repurposing-drugs-in-oncology-redo-selective-pde5-inhibitors-as-anti-cancer-agents.php
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