While Focus Of Study Was Sildenafil, The Active Ingredient Of Viagra, Melanoma Risk Likely Increased By Vardenafil (Levitra) And Tadalafil (Cialis) Also
(Posted by Tom Lamb at DrugInjuryWatch.com)
The latest medical research results about the link between melanoma skin cancer and Viagra (sildenafil) was published March 10, 2016 in the medical journal Cell Reports.
One of the most significant take-away points from this new medical article about the increased risk of melanoma associated with Viagra is that this skin cancer side effect most likely applies to Cialis (tadalafil) and Levitra (vardenafil), also.
This March 2016 Cell Reports article is titled "Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth".
From the Summary view for the online version of this medical journal report we get these Highlights:
• Melanoma cells express a cGMP signaling pathway involving PDE5
• The cGMP pathway promotes MAPK signaling and melanoma cell growth and migration
• PDE5 degrades cGMP and thus acts as a brake on the growth-promoting cGMP pathway
• The PDE5 blocker [Viagra (sildenafil)] releases the PDE5 brake, leading to increased tumor growth
For the in-depth findings we take you to the Full Text view of this article on the Cell Reports website.
To start, here is some contextual from the "Introduction" section:
In this study [(Arozarena et al., 2011).], melanoma cell invasion could be induced in vitro by the PDE5 inhibitor [Viagra (sildenafil)], which is clinically used to treat erectile dysfunction and pulmonary hypertension. Moreover, a recent prospective cohort study in men in the United States indicated that [Viagra (sildenafil)] use may be linked to an increased risk of developing melanoma (Li et al., 2014)....
The aim of the present study was to characterize the expression and functional role of components of the cGMP signaling system in melanoma cells of murine and human origin. We have identified a cGMP pathway that promotes MAPK signaling and melanoma growth in vitro and in vivo. Importantly, it was found that the growth-promoting cGMP pathway could be potentiated pharmacologically by treatment of melanoma cells or mice with [Viagra (sildenafil)]....
We conclude that, similar to murine melanoma cells, human melanoma cells can express a growth-promoting cGMP pathway that is also responsive to pharmacological stimulation with [Viagra (sildenafil)].
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And for the facts and analysis involved with the recent Viagra - melanoma medical research we continue on to the "Discussion" section, from which we get these points:
- ... our pharmacological experiments with PDE5 inhibitors [Viagra (sildenafil), Cialis (tadalafil), and Levitra (vardenafil)] demonstrated that PDE5 contributes to the degradation of cGMP and is, thus, an important “brake” for cGMP signaling in melanoma cells. Stimulation of melanoma cells with the physiological agonist CNP resulted in increased growth as determined by conventional endpoint assays as well as by impedance-based real-time monitoring of living cells.
- Importantly, the PDE5 brake can also be released pharmacologically by sildenafil, thus explaining the pro-melanoma effects of this drug.
- Our data together with the findings of Arozarena et al. (2011)) raise concerns that the use of sildenafil (Viagra) or other PDE5 inhibitors like vardenafil (Levitra) or tadalafil (Cialis) could promote melanoma in humans. These drugs are the first-line therapy for most men with erectile dysfunction. Indeed, a recent long-term cohort study that included 14,912 men in the United States indicated that men who used [Viagra (sildenafil)] for erectile dysfunction had a significantly elevated risk of melanoma (Li et al., 2014). The link between [Viagra (sildenafil)] and melanoma development is further supported by the finding that PDE5 inhibitors promote melanin synthesis (Zhang et al., 2012), which may exacerbate melanoma development (Noonan et al., 2012). PDE5 inhibitors are also used for the treatment of benign prostate hyperplasia and pulmonary arterial hypertension, and there is a tremendous growth of preclinical and clinical studies exploring new applications of PDE5 inhibitors, such as the management of cardiovascular diseases, diabetes, and even cancer (Das et al., 2015, Ghofrani et al., 2006, Shi et al., 2011).
Based on these points, it seems two other brand name ED drugs, Staxyn (vardenafil) and Stendra (avanafil), are probably associated with an increased risk of melanoma skin cancer, too.
Furthermore, Cialis (tadalafil) is also prescribed sometimes when doctors see the signs and symptoms of benign prostatic hyperplasia (BPH). And two other phosphodiesterase 5 (PDE5) inhibitors, Revatio (sildenafil) and Adcirca (tadalafil), are prescribed for the treatment of pulmonary arterial hypertension (PAH).
Returning to this most recent Viagra - melanoma medical article, here is the authors' conclusion:
Taken together, this study has uncovered a previously unknown cGMP-cGKI signaling cascade in murine and human melanoma cells. Activation of this pathway promotes tumor cell growth in vitro and in vivo. This pathway also provides a mechanism for the reported pro-melanoma effects of [Viagra (sildenafil)] and it could be an interesting therapeutic target in melanoma.
We will continue to watch for developments concerning the apparent link between Viagra and melanoma skin cancer, which seems to be a side effect of Cialis, Levitra, Staxyn, Stendra, Revatio, and Adcirca, too.
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