scholarly journals Clinical Perspectives of ERCC1 in Bladder Cancer

2020 ◽  
Vol 21 (22) ◽  
pp. 8829
Author(s):  
Konstantinos Koutsoukos ◽  
Angeliki Andrikopoulou ◽  
Nikos Dedes ◽  
Flora Zagouri ◽  
Aristotelis Bamias ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Dna Adducts ◽  
Protein Function ◽  
Excision Repair ◽  
Locally Advanced ◽  
Platinum Resistance ◽  
Nucleotide Polymorphisms ◽  
Repair Capacity ◽  
Dna Repair Capacity

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.

The Role of Chemotherapy in Locally Advanced and Metastatic Bladder Cancer

2021 ◽  
pp. 445-465
Author(s):  
Sanchia S. Goonewardene ◽  
Karen Ventii ◽  
Amit Bahl ◽  
Raj Persad ◽  
Hanif Motiwala ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Locally Advanced ◽  
Metastatic Bladder Cancer

Neoadjuvant Chemotherapy Plus Cystectomy Compared With Cystectomy Alone for Locally Advanced Bladder Cancer

2021 ◽  
pp. 141-146
Author(s):  
Vikram M. Narayan
Keyword(s):  
Adverse Effect ◽  
Overall Survival ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Randomized Study ◽  
Locally Advanced ◽  
Common Adverse Effect ◽  
Advanced Bladder Cancer ◽  
Muscle Invasive

This study summarizes a landmark study on the role of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in patients with muscle-invasive bladder cancer. This randomized study of M-VAC plus cystectomy versus cystectomy alone suggested improved overall survival in patients receiving neoadjuvant therapy. Severe granulocytopenia was a common adverse effect in the chemotherapy group, but no deaths were attributed to chemotherapy.

Abstract 5367: DNA repair capacity, gene expression and epigenomic profiles in bladder cancer

2014 ◽  
Author(s):  
Barbara Pardini ◽  
Alessandra Allione ◽  
Simonetta Guarrera ◽  
Valentina Turinetto ◽  
Giovanni Fiorito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Dna Repair ◽  
Repair Capacity ◽  
Dna Repair Capacity

The role of TP53 PRO47SER and ARG72PRO single nucleotide polymorphisms in the susceptibility to bladder cancer

2011 ◽  
Vol 29 (3) ◽  
pp. 291-294 ◽  
Author(s):  
Luis Eduardo Murgel de Castro Santos ◽  
Ana Carolina Trindade Guilhen ◽  
Renato Alves de Andrade ◽  
Larissa Garcia Sumi ◽  
Laura S. Ward
Keyword(s):  
Bladder Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Phase I/II trial for evaluation of the role of gemcitabine as a radiosensitizer in locally advanced bladder cancer in Egypt

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 4727-4727
Author(s):  
A. O. Abd-Elghany ◽  
H. T. Kamal ◽  
K. A. El Ghamrawy ◽  
Y. Gouda ◽  
W. O. Arafat
Keyword(s):  
Bladder Cancer ◽  
Phase I ◽  
Locally Advanced ◽  
Advanced Bladder Cancer

scholarly journals DNA repair-based classification of melanoma cell lines reveals an effect of mutations in BRAF and NRAS driver genes on DNA repair capacity

2020 ◽  
Author(s):  
Sylvie Sauvaigo ◽  
Manel Benkhiat ◽  
Florian Braisaz ◽  
Julien Girard ◽  
Sarah Libert ◽  
...  
Keyword(s):  
Dna Repair ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Excision Repair ◽  
Mapk Pathway ◽  
Repair Capacity ◽  
Signaling Mechanism ◽  
Dna Repair Capacity ◽  
Melanoma Cell Lines

AbstractMelanoma, the most serious form of skin cancer, frequently involves the dysregulation of key signaling pathways. Treatment strategies presently target the MAPK/ERK pathway, which is overactive in melanomas due in part to BRAF and NRAS mutations, and involve inhibitors against mutated BRAF (vemurafenib or dabrafenib) or MEK kinases (cobimetinib or trametinib), or a combination of the two. Using an established biochip technology, we assessed base excision repair (BER) and nucleotide excision repair (NER) activities in a collection of BRAF mutated (A-375, Colo 829, HT-144, Malme-3M, SK-mel5, SK-mel24 and SK-mel28) and NRAS mutated (M18, MZ2 and SK-mel2) melanoma cell lines, as well as wild-type controls (A7, CHL-1). We evaluated both basal activities (i.e., without treatment) and repair capacities after treatment with vemurafenib or cobimetinib alone, or in combination. Our results indicate that globally the DNA repair capacity of the cell lines was determined by the mutation status of the BRAF and NRAS genes, indicating that the MAPK pathway participates in the regulation of both BER and NER. Treatment of BRAF mutated melanoma cells with vemurafenib alone or the vemurafenib/cobimetinib combination, but not cobimetinib alone, led to reduced DNA repair capacity in about 60% of the BRAF mutated samples, indicating that signaling pathway inhibition can alter DNA repair activity. Upregulation of some DNA repair activities was also observed in several of the treated samples, suggesting activation of compensatory signaling pathways upon treatment. The data collectively indicate that mutations in the BRAF and NRAS genes exert distinct regulatory effects on the excision/synthesis steps of the BER and NER pathways and that targeted pharmacological inactivation of the signaling mechanism can translate into specific consequences in DNA repair capacity. The heterogeneity of the responses reported herein could help define subtypes of melanoma that are associated with resistance to targeted therapies.

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