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The Role of PDE3A in Cancer
Shengyu Pu1, Qihe Zhang2, Mi Miao2
1Dept. of Nuclear Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
ACS Omega
|February 23, 2026
Summary
Phosphodiesterase 3A (PDE3A) is overexpressed in many cancers, driving tumor growth, metastasis, and drug resistance. Inhibiting PDE3A shows promise for novel cancer therapies, especially for resistant tumors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Phosphodiesterase 3A (PDE3A) is crucial for regulating cyclic nucleotide levels, impacting platelet activation, cardiac function, and vascular smooth muscle cell proliferation.
- Emerging evidence highlights PDE3A's significant role in the development and progression of various malignant tumors.
Purpose of the Study:
- To investigate the multifaceted regulation of PDE3A expression in cancer.
- To elucidate PDE3A's functional mechanisms in tumor cell proliferation, metastasis, and chemotherapy resistance.
- To evaluate PDE3A as a potential therapeutic target for cancer treatment.
Main Methods:
- A systematic review of 221 PubMed-indexed articles was performed.
- Analysis focused on PDE3A expression, its regulatory pathways, and its role in cancer hallmarks.
- Investigated PDE3A inhibition strategies and therapeutic potential.
Main Results:
- Aberrant PDE3A overexpression is observed in multiple cancers, including gastrointestinal stromal tumors, hepatocellular carcinoma, and breast cancer.
- PDE3A expression is regulated by genetic, epigenetic, and post-translational mechanisms, influencing cancer stem cell traits, metastasis, and drug resistance via signaling pathways like NF-κB and YAP/TEAD.
- PDE3A inhibitors, alone or in combination with chemotherapy, demonstrate significant antitumor efficacy, particularly in refractory cancers.
Conclusions:
- Aberrant PDE3A expression is a key driver of tumorigenesis, progression, and therapeutic resistance.
- Targeting PDE3A through inhibitors or molecular agents presents a promising therapeutic strategy for various cancers, especially those resistant to conventional chemotherapy.
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