Pros and Cons of Pharmacological Manipulation of cGMP-PDEs in the Prevention and Treatment of Breast Cancer

Iorio, Patrizia Di; Ronci, Maurizio; Giuliani, Patricia; Caciagli, Francesco; Ciccarelli, Renata; Caruso, Vanni; Beggiato, Sarah; Zuccarini, Mariachiara

doi:10.3390/ijms23010262

Cited by 15 publications

(7 citation statements)

References 120 publications

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“…Intracellular cGMP-activated cation channels are proteins activated by the signaling molecule cGMP, which allow ions to enter cells ( Biel and Michalakis, 2009 ). Dysregulation of these channels has been linked to the development of various types of cancer, including breast, prostate, and ovarian cancer ( Di Iorio et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

A Boolean-based machine learning framework identifies predictive biomarkers of HSP90-targeted therapy response in prostate cancer

Shin

Centenera²,

Hodgson³

et al. 2023

Front. Mol. Biosci.

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Precision medicine has emerged as an important paradigm in oncology, driven by the significant heterogeneity of individual patients’ tumour. A key prerequisite for effective implementation of precision oncology is the development of companion biomarkers that can predict response to anti-cancer therapies and guide patient selection for clinical trials and/or treatment. However, reliable predictive biomarkers are currently lacking for many anti-cancer therapies, hampering their clinical application. Here, we developed a novel machine learning-based framework to derive predictive multi-gene biomarker panels and associated expression signatures that accurately predict cancer drug sensitivity. We demonstrated the power of the approach by applying it to identify response biomarker panels for an Hsp90-based therapy in prostate cancer, using proteomic data profiled from prostate cancer patient-derived explants. Our approach employs a rational feature section strategy to maximise model performance, and innovatively utilizes Boolean algebra methods to derive specific expression signatures of the marker proteins. Given suitable data for model training, the approach is also applicable to other cancer drug agents in different tumour settings.

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Section: Discussionmentioning

confidence: 99%

A Boolean-based machine learning framework identifies predictive biomarkers of HSP90-targeted therapy response in prostate cancer

Shin

Centenera²,

Hodgson³

et al. 2023

Front. Mol. Biosci.

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“…This suggests that the expression of PDE11A can regulate the development of glioblastoma in patients. Other PDEs (PDE5, PDE8, and PDE10) are also involved in cancer cell proliferation; various mutations have been described ( 96 – 98 ). Therefore, PDE11A and other PDEs fail to act as regulators of cAMP and cGMP, affecting the growth and development of cancer cells.…”

Section: Pde11a and Tumorsmentioning

confidence: 99%

Functional characteristics and research trends of PDE11A in human diseases (Review)

Kong

Lee

et al. 2022

Mol Med Rep

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caMP and cGMP are important secondary messengers involved in cell regulation and metabolism driven by the G protein-coupled receptor. caMP is converted via adenylyl cyclase (ac) and activates protein kinase a to phosphorylate intracellular proteins that mediate specific responses. cAMP signaling serves a role at multiple steps in tumorigenesis. The level of caMP is increased in association with cancer cell formation through activation of ac-stimulatory G protein by mutation. Phosphodiesterases (Pdes) hydrolyze caMP and cGMP to aMP and GMP. Pdes are composed of 11 families, and each can hydrolyze caMP and cGMP or both caMP and cGMP. Pdes perform various roles depending on their location and expression site, and are involved in several diseases, including male erectile dysfunction, pulmonary hypertension, alzheimer's disease and schizophrenia. Pde11a is the 11th member of the Pde family and is characterized by four splice variants with varying tissue expression and n-terminal regulatory regions. among tissues, the expression of Pde11a was highest in the prostate, and it was also expressed in hepatic skeletal muscle, pituitary, pancreas and kidney. Pde11a is the first PDE associated with an adrenocortical tumor associated genetic condition. in several studies, three Pde11a mutations have been reported in patients with cushing syndrome with primary pigmented nodular adrenocortical disease or isolated micronodular adrenocortical disease without other genetic defects. it has been reported that an increase in Pde11a expression affects the proliferation of glioblastoma and worsens patient prognosis. The present mini-review summarizes the location of Pde11a expression, the impact of structural differences and disease relevance. Contents1. introduction 2. caMP/cGMP-dependent signaling 3. Phosphodiesterase family 4. Pde11a and tumors 5. other diseases cause by Pde11a 6. Further focus for Pde11a

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“…Di Iorio et al reviewed the possible role of cGMP-PDE in breast cancer and discussed the potential application of cGMP-PDE inhibitors. For this, the notable and controversial studies concerning an off-label use of these inhibitors in cancer therapy are summarized [ 10 ].…”

Section: Communicationmentioning

confidence: 99%

Editorial of the Special Issue: cGMP-Signaling in Cells and Tissues: Molecular, Functional and Pharmacological Aspects

Schlossmann

2022

IJMS

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Pros and Cons of Pharmacological Manipulation of cGMP-PDEs in the Prevention and Treatment of Breast Cancer

Cited by 15 publications

References 120 publications

A Boolean-based machine learning framework identifies predictive biomarkers of HSP90-targeted therapy response in prostate cancer

A Boolean-based machine learning framework identifies predictive biomarkers of HSP90-targeted therapy response in prostate cancer

Functional characteristics and research trends of PDE11A in human diseases (Review)

Editorial of the Special Issue: cGMP-Signaling in Cells and Tissues: Molecular, Functional and Pharmacological Aspects

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