Yu-Ling Kou, Yu-Jie Liu, and colleagues have published their article entitled “SB431542, a Selective Inhibitor of the TGF-β Type I Receptor, Enhances Doxorubicin Antitumor Activity via p63 Activation in Mutant p53 Breast Cancer Cells” in Volume 30, Issue 12 of Frontiers in Bioscience–Landmark (FBL) (https://www.imrpress.com/journal/FBL/30/12/10.31083/FBL45389).

 

   

    Bi-He Cai | PhD
    School of Medicine, I-Shou University, Kaohsiung, Taiwan
      

 

We are honored to invite one of the corresponding authors, Dr. Bi-He Cai, to provide his expert interpretation of the article. Dr. Bi-He Cai is an Associate Professor in the School of Medicine at I-Shou University, Kaohsiung, Taiwan. He leads the p53 Family Laboratory in Taiwan, where his research focuses on the roles of p53 family proteins in cancer progression and therapeutic resistance, aiming to identify novel targets for improved cancer therapy.

 

Author's Interpretation

In this study, we focused on breast cancer cells carrying TP53 mutations, which are more difficult to treat because mutated TP53 reduces the effectiveness of chemotherapy drugs such as doxorubicin. We asked whether blocking the TGF-β signal pathway could improve the chemotherapy response in these resistant cancer cells, using SB431542, a selective inhibitor of the TGF-β type I receptor.

SB431542 alone showed minimal cytotoxicity effects; however, when combined with doxorubicin, it markedly enhanced cancer cell death compared with doxorubicin alone. To understand how this effect occurs, we identified p63, a member of the p53 family, as a key mediator of this effect. Even in the absence of functional p53, p63 can activate cell-death pathways. Our data showed that TGF-β signaling suppresses p63 activity, and inhibition of this pathway by SB431542 restored p63 activation, leading to apoptosis.

Notably, this synergistic effect was particularly pronounced in mutant TP53 breast cancer cells, including aggressive subtypes such as triple-negative breast cancer. Overall, our findings suggest that inhibition of TGF-β signaling can overcome chemotherapy resistance by activating p63, thereby enhancing the antitumor activity of doxorubicin in TP53-mutated breast cancers.

 

Original Article:

SB431542, a Selective Inhibitor of the TGF-β Type I Receptor, Enhances Doxorubicin Antitumor Activity via p63 Activation in Mutant p53 Breast Cancer Cells: https://www.imrpress.com/journal/FBL/30/12/10.31083/FBL45389

 

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