Recent advances of Phosphodiesterase 4B in cancer

ABSTRACT

Introduction

Phosphodiesterase 4B (PDE4B) is a crucial enzyme in the phosphodiesterases (PDEs), acting as a regulator of cyclic adenosine monophosphate (cAMP). It is involved in cancer process through PDE4B/cAMP signaling pathway. Cancer occurs and develops with the regulation of PDE4B in the body, suggesting that PDE4B is a promising therapeutic target.

Areas covered

This review covereed the function and mechanism of PDE4B in cancer. We summarized the possible clinical applications of PDE4B, and highlighted the possible ways to develop clinical applications of PDE4B inhibitors. We also discussed some common PDEs inhibitors, and expected the development of combined targeting PDE4B and other PDEs drugs in the future.

Expert opinion

The existing research and clinical data can strongly prove the role of PDE4B in cancer. PDE4B inhibition can effectively increase cell apoptosis, inhibit cell proliferation, transformation, migration, etc., indicating that PDE4B inhibition can effectively inhibit the development of cancer. Other PDEs may antagonize or coordinate this effect. As for the further study on the relationship between PDE4B and other PDEs in cancer, it is still a challenge to develop multi-targeted PDEs inhibitors.

KEYWORDS:

• Cancer
• cyclic adenosine monophosphate
• inhibitors
• phosphodiesterases
• phosphodiesterase 4B

Article highlights

• PDE4B is a key regulator of intracellular cAMP levels by controlling degradation rate of cAMP in PDEs.

• The abnormal regulation of PDE4B in several cancer types is related to the inhibition of apoptosis, promotion of proliferation, transformation, and metastasis of cancer cells.

• Clinical data show that PDE4B plays an important role in the diagnosis, classification, treatment, and prognosis of cancer.

• Due to the lack of specificity of PDE4B inhibitors, only parts of them are put into clinical trials.

• PDE4B inhibition can cause changes in other PDEs levels, which plays a coordinating or antagonistic role in the treatment of diseases.

• In the future, the combination of PDEs inhibition may be more effective in the treatment of cancer.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by Clinical Medical research transformation Project of Anhui Province (202204295107020023), Natural Science Project of Anhui Province (2208085MH252), Health research Project of Anhui Province (AHWJ2022b012), Natural Science Project of Anhui Province (2208085MH203), and Anhui Medical University ‘Three Complete Education’ Comprehensive Reform Pilot Project (2021xsqyr05).