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Updated: May 13, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Molecular markers of therapeutic resistance in breast cancer
1Department of Surgery, Shanghai First People's Branch Hospital, Shanghai Jiaotong University, Shanghai 200081, China.
Abstract:
Resistance to chemotherapy and endocrine therapy is a serious obstacle in the treatment of breast cancer. Highly specific biomarkers for predicting therapeutic resistance have not yet been identified. In this study, the amounts of aldehyde dehydrogenase 1, cleaved caspase 3, cyclooxygenase 2, phosphorylated Akt, Ki-67, and H2AX proteins were measured by immunohistochemical staining in 113 breast cancer tissues, and their predictive ability for therapeutic resistance was investigated. The patients were receiving chemotherapy (n = 30), endocrine therapy (n = 22), or combined chemotherapy and endocrine therapy (n = 61). Expression of aldehyde dehydrogenase 1, cleaved caspase 3, and cyclooxygenase 2 correlated significantly with a higher relapse rate (P < .05 or P < .01) and shorter survival (P < .01 or P < .001) in triple-negative patients receiving chemotherapy. In addition, cyclooxygenase 2 expression was an independent predictor of a poor prognosis (P < .05). On the other hand, aldehyde dehydrogenase 1 expression correlated significantly with shorter survival in patients receiving combined therapy (P < .01) but showed no association with relapse. No correlation was observed between Ki-67, phosphorylated Akt, and H2AX expression and survival or relapse in any group of patients. These data suggest that aldehyde dehydrogenase 1, cleaved caspase 3, and cyclooxygenase 2 are useful markers for therapeutic resistance in breast cancer.
Insights
New biomarkers, including aldehyde dehydrogenase 1, cleaved caspase 3, and cyclooxygenase 2, show promise for predicting breast cancer treatment resistance and patient survival outcomes.
Area of Science:
- Oncology
- Biomarker Research
- Cancer Therapeutics
Background:
- Therapeutic resistance to chemotherapy and endocrine therapy presents a significant challenge in breast cancer management.
- The identification of specific biomarkers to predict treatment resistance remains an unmet clinical need.
Purpose of the Study:
- To investigate the predictive value of aldehyde dehydrogenase 1 (ALDH1), cleaved caspase 3 (CC3), cyclooxygenase 2 (COX-2), phosphorylated Akt (p-Akt), Ki-67, and H2AX protein expression for therapeutic resistance in breast cancer patients.
- To assess the correlation of these protein expressions with relapse rates and survival outcomes across different treatment modalities.
Main Methods:
- Immunohistochemical staining was employed to quantify the expression levels of target proteins in 113 breast cancer tissue samples.
- Patients received chemotherapy, endocrine therapy, or a combination of both.
- Statistical analyses were performed to evaluate the association between protein expression and clinical outcomes, including relapse and survival.
Main Results:
- ALDH1, CC3, and COX-2 expression significantly correlated with increased relapse rates and reduced survival in triple-negative breast cancer patients undergoing chemotherapy.
- COX-2 was identified as an independent predictor of poor prognosis.
- ALDH1 expression was associated with shorter survival in patients receiving combined therapy, but not with relapse.
Conclusions:
- ALDH1, CC3, and COX-2 show potential as valuable biomarkers for predicting therapeutic resistance in breast cancer.
- These findings may aid in personalizing treatment strategies and improving patient outcomes by identifying individuals at higher risk of resistance.
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