Developing a Phosphodiesterase 10A Inhibitor as a Novel Therapeutic Agent for Triple-Negative Breast Cancer

Authors

• Mrityunjoy Biswas, LSU Health Sciences Center – New OrleansFollow
• Md Manirujjaman, LSU Health Sciences Center – New OrleansFollow
• Jovanny Zabaleta, LSU Health Sciences Center – New OrleansFollow
• Dorota Wyczechowska, LSU Health Sciences Center – New OrleansFollow
• Jone Garai, LSU Health Sciences Center – New OrleansFollow
• Qingzhao Yu, LSU Health Sciences Center – New OrleansFollow
• Luis Del Valle, LSU Health Sciences Center – New OrleansFollow
• Samarpan Majumder, LSU Health Sciences Center – New OrleansFollow
• Timothy Kayes, LSU Health Sciences Center – New OrleansFollow
• Xi Chen, Auburn University, Auburn, AL
• Adam B. Keeton, Auburn University, Auburn, AL
• Lucio Miele, LSU Health Sciences Center – New OrleansFollow
• Yulia Y. Maxuitenko, Auburn University, Auburn, AL
• Nan Li, The University of Alabama at Birmingham, Birmingham, AL
• Gary A. Piazza, Auburn University, Auburn, AL
• Fokhrul Hossain, LSU Health Sciences Center – New OrleansFollow

Document Type

Article

Publication Date

7-30-2026

Publication Title

Cells

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited therapeutic options for patients at high risk of disease recurrence and metastasis. The cyclic nucleotide-degrading enzyme, phosphodiesterase 10A (PDE10), that hydrolyzes both cAMP and cGMP has been previously reported to be expressed in multiple cancers and regulates key cellular signaling pathways involved in cancer cell proliferation, survival, and maintenance of stem cell-like properties. We found that PDE10 overexpression was associated with poor relapse-free survival of TNBC patients and identified its potential as a therapeutic target for TNBC using a novel inhibitor, ADT-030. Our results showed that ADT-030 inhibited the growth of TNBC cells, reduced colony-forming efficiency and enhanced the therapeutic efficacy of paclitaxel. A TNBC mouse model demonstrated that oral administration of ADT-030 significantly suppressed syngeneic tumor growth and enhanced the antitumor efficacy of paclitaxel. ADT-030 treatment altered differentially expressed genes (DEGs), signaling pathways, and cellular processes. Overall, our findings suggest that ADT-030, as a monotherapy or in combination with standard-of-care chemotherapy, may be an effective therapeutic approach for TNBC. Further studies are warranted to better understand the oncogenic role of PDE10 in TNBC and the mechanisms by which ADT-030 modulates the tumor microenvironment (TME) and enhances chemotherapy response.

PubMed ID

42587783

Volume

15

Issue

15

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Biswas, Mrityunjoy; Manirujjaman, Md; Zabaleta, Jovanny; Wyczechowska, Dorota; Garai, Jone; Yu, Qingzhao; Del Valle, Luis; Majumder, Samarpan; Kayes, Timothy; Chen, Xi; Keeton, Adam B.; Miele, Lucio; Maxuitenko, Yulia Y.; Li, Nan; Piazza, Gary A.; and Hossain, Fokhrul, "Developing a Phosphodiesterase 10A Inhibitor as a Novel Therapeutic Agent for Triple-Negative Breast Cancer" (2026). School of Graduate Studies Faculty Publications. 658.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/658
10.3390/cells15151374