Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last several decades, many new drugs that target molecular pathways in carcinogenesis and the inflammatory immune system have been developed, resulting in substantial improvements in the treatment of many malignancies and inflammatory conditions. However, an increasingly widespread deployment of these new drugs has revealed an increased tendency for patients to develop skin malignancy in some instances and questions of possible association between their use and skin cancer. Specifically, increased skin cancer risk has been reported in association with BRAF inhibitors, sonic hedgehog-inhibiting agents, Janus kinase (JAK) inhibitors, and phosphodiesterase 5 (PDE-5) inhibitors. We review the literature on each drug class and its association with skin malignancy, as well as recommendations regarding drug use, surveillance, and treatment.
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PMID:Systemic medications linked to an increased risk for skin malignancy. 3177 4

The repurposing of existing drugs has emerged as an attractive additional strategy to the development of novel compounds in the fight against cancerous diseases. Inhibition of phosphodiesterase 5 (PDE5) has been claimed as a potential approach to target various cancer subtypes in recent years. However, data on the treatment of tumors with PDE5 inhibitors as well as the underlying mechanisms are as yet very scarce. Here, we report that treatment of tumor cells with low concentrations of Sildenafil was associated with decreased cancer cell proliferation and augmented apoptosis in vitro and resulted in impaired tumor growth in vivo. Notably, incubation of cancer cells with Sildenafil was associated with altered expression of HSP90 chaperone followed by degradation of protein kinase D2, a client protein previously reported to be involved in tumor growth. Furthermore, the involvement of low doses of PU-H71, an HSP90 inhibitor currently under clinical evaluation, in combination with low concentrations of Sildenafil, synergistically and negatively impacted on the viability of cancer cells in vivo. Taken together, our study suggests that repurposing of already approved drugs, alone or in combination with oncology-dedicated compounds, may represent a novel cancer therapeutic strategy.
Carcinogenesis 2020 Oct 15
PMID:Sildenafil triggers tumor lethality through altered expression of HSP90 and degradation of PKD2. 3191 3


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