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

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 inhibitors as off-label adjuvants in cancer therapy.

Automated summary

The cyclic nucleotides, cAMP and cGMP, act as second messengers in both normal and tumor cells, playing a crucial role in translating extracellular signals to intracellular responses. Inhibition of cGMP-hydrolyzing phosphodiesterases (PDEs) has shown potential as a therapeutic approach for cancer by regulating cell growth, apoptosis, and sensitivity to chemotherapy. However, the use of PDE5 inhibitors in breast cancer treatment remains controversial.