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Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis
Published on: May 12, 2019
Clinical Perspectives of ERCC1 in Bladder Cancer
Konstantinos Koutsoukos1, Angeliki Andrikopoulou1, Nikos Dedes1
1Department of Clinical Therapeutics, Alexandra Hospital, Medical School, 11528 Athens, Greece.
Abstract:
ERCC1 is a key regulator of nucleotide excision repair (NER) pathway that repairs bulky DNA adducts, including intrastrand DNA adducts and interstrand crosslinks (ICLs). Overexpression of ERCC1 has been linked to increased DNA repair capacity and platinum resistance in solid tumors. Multiple single nucleotide polymorphisms (SNPs) have been detected in ERCC1 gene that may affect ERCC1 protein expression. Platinum-based treatment remains the cornerstone of urothelial cancer treatment. Given the expanding application of neoadjuvant and adjuvant chemotherapy in locally advanced bladder cancer, there is an emerging need for biomarkers that could distinguish potential responders to cisplatin treatment. Extensive research has been done regarding the prognostic and predictive role of ERCC1 gene expression and polymorphisms in bladder cancer. Moreover, novel compounds have been recently developed to target ERCC1 protein function in order to maximize sensitivity to cisplatin. We aim to review all the existing literature regarding the role of the ERCC1 gene in bladder cancer and address future perspectives for its clinical application.
Insights
The ERCC1 gene influences DNA repair and platinum resistance in bladder cancer. Understanding ERCC1 expression and polymorphisms may predict treatment response and guide future cisplatin-based therapies.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The ERCC1 gene is crucial for nucleotide excision repair (NER), a pathway vital for correcting DNA damage.
- ERCC1 overexpression is associated with enhanced DNA repair and resistance to platinum-based chemotherapy in solid tumors.
- Single nucleotide polymorphisms (SNPs) in the ERCC1 gene may impact its protein expression and function.
Purpose of the Study:
- To review the existing literature on the role of the ERCC1 gene in bladder cancer.
- To explore the prognostic and predictive significance of ERCC1 gene expression and polymorphisms in urothelial carcinoma.
- To discuss future clinical applications of ERCC1 as a biomarker and therapeutic target in bladder cancer.
Main Methods:
- Literature review of studies investigating ERCC1 in bladder cancer.
- Analysis of research on ERCC1 gene expression levels and its association with treatment outcomes.
- Examination of studies focusing on ERCC1 polymorphisms and their impact on cisplatin sensitivity.
Main Results:
- ERCC1 expression levels and specific polymorphisms have shown potential as predictive biomarkers for platinum-based chemotherapy response in bladder cancer.
- Elevated ERCC1 expression is frequently linked to resistance to cisplatin and other platinum agents.
- Certain ERCC1 SNPs may influence patient outcomes and treatment efficacy.
Conclusions:
- ERCC1 plays a significant role in DNA repair and chemoresistance in bladder cancer.
- ERCC1 gene expression and polymorphisms hold promise as biomarkers for personalizing cisplatin treatment strategies.
- Targeting ERCC1 function presents a potential avenue for overcoming platinum resistance and improving therapeutic outcomes.
