Targeting lineage plasticity overcomes chemoresistance
1Department of Pathology and Tumor Biology, Graduate School of Medicine, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
Cancer Cell
|September 13, 2022
Summary
Chemoresistant muscle-invasive bladder cancer shows partial squamous differentiation. Targeting Cathepsin H reverses this, promoting tumor suppression and full squamous differentiation.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Muscle-invasive bladder cancer (MIBC) often develops chemoresistance.
- Chemoresistance in MIBC is linked to partial squamous differentiation, a process known as semi-squamatization.
Purpose of the Study:
- To investigate the mechanism behind chemoresistance in muscle-invasive bladder cancer.
- To identify therapeutic targets that can overcome chemotherapy-induced partial squamous differentiation.
Main Methods:
- Analysis of chemoresistant bladder cancer models.
- Investigating the role of Cathepsin H in squamous differentiation.
- Evaluating the efficacy of Cathepsin H targeting in preclinical models.
Main Results:
- Chemoresistant muscle-invasive bladder cancer exhibits partial squamous differentiation.
- Cathepsin H plays a critical role in mediating chemotherapy-induced semi-squamatization.
- Targeting Cathepsin H effectively promotes terminal squamous differentiation.
Conclusions:
- Partial squamous differentiation is a mechanism of chemoresistance in muscle-invasive bladder cancer.
- Cathepsin H is a viable therapeutic target to overcome chemoresistance.
- Targeting Cathepsin H can restore tumor suppressor functions and promote tumor regression.
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