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Pros and cons of pharmacological manipulation of cGMP-PDEs in the prevention and treatment of breast cancer
journal contributionposted on 2023-05-23, 00:04 authored by Di Iorio, P, Ronci, M, Giuliani, P, Caciagli, F, Ciccarelli, R, Vanni CarusoVanni Caruso, Beggiato, S, Zuccarini, M
The cyclic nucleotides, cAMP and cGMP, are ubiquitous second messengers responsible for translating extracellular signals to intracellular biological responses in both normal and tumor cells. When these signals are aberrant or missing, cells may undergo neoplastic transformation or become resistant to chemotherapy. cGMP-hydrolyzing phosphodiesterases (PDEs) are attracting tremendous interest as drug targets for many diseases, including cancer, where they regulate cell growth, apoptosis and sensitization to radio- and chemotherapy. In breast cancer, PDE5 inhibition is associated with increased intracellular cGMP levels, which is responsible for the phosphorylation of PKG and other downstream molecules involved in cell proliferation or apoptosis. In this review, we provide an overview of the most relevant studies regarding the controversial role of PDE inhib-itors as off-label adjuvants in cancer therapy.
Publication titleInternational Journal of Molecular Sciences
Department/SchoolSchool of Pharmacy and Pharmacology
PublisherMolecular Diversity Preservation International
Place of publicationMatthaeusstrasse 11, Basel, Switzerland, Ch-4057