How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme

Sanati, Mehdi; Aminyavari, Samaneh; Mollazadeh, Hamid; Bibak, Bahram; Mohtashami, Elmira; Afshari, Amir R.

doi:10.1007/s43440-021-00349-6

Cited by 7 publications

(3 citation statements)

References 192 publications

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“…A plethora of preclinical and clinical studies were conducted over the past 20 years to evaluate the role of PDE5-Is either as a single treatment or in combination therapy for various FDA-approved or emerging clinical conditions. These studies have been extensively discussed in several previous reviews [ 17 , 23 , 76 , 122 , 123 , 283 , 284 , 285 , 286 , 287 ]; thus, we herein present an update of the clinical trials status of PDE5-Is in the past five years (summarized in Table 2 ). Focus was mainly directed to registered trials in (accessed on 1 August 2023) that are complete with published results.…”

Section: Recent Update On Clinical Trials Involving Pde5 Inhibitorsmentioning

confidence: 99%

Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives

ElHady,

El-Gamil,

Abdel-Halim

et al. 2023

Pharmaceuticals

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Phosphodiesterase 5 (PDE5) inhibitors presented themselves as important players in the nitric oxide/cGMP pathway, thus exerting a profound impact on various physiological and pathological processes. Beyond their well-known efficacy in treating male erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), a plethora of studies have unveiled their significance in the treatment of a myriad of other diseases, including cognitive functions, heart failure, multiple drug resistance in cancer therapy, immune diseases, systemic sclerosis and others. This comprehensive review aims to provide an updated assessment of the crucial role played by PDE5 inhibitors (PDE5-Is) as disease-modifying agents taking their limiting side effects into consideration. From a medicinal chemistry and drug discovery perspective, the published PDE5-Is over the last 10 years and their binding characteristics are systemically discussed, and advancement in properties is exposed. A persistent challenge encountered with these agents lies in their limited isozyme selectivity; considering this obstacle, this review also highlights the breakthrough development of the recently reported PDE5 allosteric inhibitors, which exhibit an unparalleled level of selectivity that was rarely achievable by competitive inhibitors. The implications and potential impact of these novel allosteric inhibitors are meticulously explored. Additionally, the concept of multi-targeted ligands is critically evaluated in relation to PDE5-Is by inspecting the broader spectrum of their molecular interactions and effects. The objective of this review is to provide insight into the design of potent, selective PDE5-Is and an overview of their biological function, limitations, challenges, therapeutic potentials, undergoing clinical trials, future prospects and emerging uses, thus guiding upcoming endeavors in both academia and industry within this domain.

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Section: Recent Update On Clinical Trials Involving Pde5 Inhibitorsmentioning

confidence: 99%

Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives

ElHady,

El-Gamil,

Abdel-Halim

et al. 2023

Pharmaceuticals

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show abstract

“…Sildenafil increased the efficacy of 5-FU and anti-PD1 therapies when combined with curcumin in vivo, and enhanced anti-tumor immunity by acting on immune cells in TME. [27][28][29] Although accumulating evidence has widely reported that PDE5 inhibitors directly inhibited the growth of tumor cells and mediated the anti-tumor immunity and improved the survival prognosis of patients with cancer, [30][31][32] few studies have focused on the anti-tumor effects of PDE5 inhibitors depending on TME-infiltrating immune cells. These various immune cells could be widely viewed as anticancer targets and play the ambivalent roles in antitumor immunity.…”

Section: Introductionmentioning

confidence: 99%

“…PDE5 inhibitors have anti‐tumor responses through reversing the immunosuppression of TME. Sildenafil increased the efficacy of 5‐FU and anti‐PD1 therapies when combined with curcumin in vivo, and enhanced anti‐tumor immunity by acting on immune cells in TME 27–29 . Although accumulating evidence has widely reported that PDE5 inhibitors directly inhibited the growth of tumor cells and mediated the anti‐tumor immunity and improved the survival prognosis of patients with cancer, 30–32 few studies have focused on the anti‐tumor effects of PDE5 inhibitors depending on TME‐infiltrating immune cells.…”

Section: Introductionmentioning

confidence: 99%

PDE5 inhibitors against cancer via mediating immune cells in tumor microenvironment: AI‐based approach for future drug repurposing exploration

Zhang,

Huang,

Feng

et al. 2024

Interdisciplinary Medicine

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Phosphodiesterase‐5 (PDE5) inhibitors are used clinically for the treatment of erectile dysfunction, pulmonary arterial hypertension, and other urological diseases. Emerging evidences have suggested the therapeutic capacity of PDE5 inhibitors as the repurposed drugs in oncology. However, the essential immune function of PDE5 inhibitors against cancer in tumor microenvironment (TME) remains unclear. This review aimed to summarize the recent advances regarding the repurposing of PDE5 inhibitors as anti‐cancer agents for cancer management to enhance the anti‐tumor immune response by mediating various immune cells, which included the myeloid‐derived suppressor cells, macrophages, T cells, fibroblasts, and natural killer cells in TME. Moreover, artificial intelligence (AI), as a new approach, is composed of traditional machine learning and deep learning methods and could be potentially used to identify the targets of immune cells in TME and predict the efficacy for repurposed drug toward malignancies. In summary, these endeavors provide novel insights into the comprehensive strategies for PDE5 inhibitors mediating immune cells against cancer and AI‐based approach for future drug repurposing exploration.

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Thymol has anticancer effects in U-87 human malignant glioblastoma cells

et al. 2022

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How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme

Cited by 7 publications

References 192 publications

Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives

Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives

PDE5 inhibitors against cancer via mediating immune cells in tumor microenvironment: AI‐based approach for future drug repurposing exploration

Thymol has anticancer effects in U-87 human malignant glioblastoma cells

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