Back to Search
Start Over
The molecular limitations of biomarker research in bladder cancer
- Source :
- World journal of urology. 37(5)
- Publication Year :
- 2018
-
Abstract
- Urothelial carcinoma of the bladder (UCB) is a common malignancy with limited systemic treatment options in advanced stages. Despite recent advances in immunotherapy, the majority of patients do not respond to these treatments. There is an unmet need for developing robust biomarkers to inform treatment decisions and identify patients who are likely to respond. A MEDLINE/PubMed literature search was performed, focusing on tissue-based and circulating biomarkers, and their potential in muscle-invasive UCB. UCB is a heterogeneous disease that consists of several clonal and subclonal populations, each with a mix of truncal and private genomic alterations. This inter- and intra-tumoral heterogeneous landscape results in the development of treatment resistance. Tumor heterogeneity also constitutes a barrier to the development of robust markers of response and resistance to chemotherapy and immunotherapy. Defects in DNA repair genes and a high tumor mutational burden independently confer sensitivity to cisplatin-based chemotherapy and checkpoint inhibitors. Oncogenic alterations such as FGFR3 mutations and fusions are associated with response to FGFR3 inhibitors. Several emerging potential biomarkers, including gene expression-based molecular subtypes, T-cell receptor clonality, and tissue- or blood-based immune-gene profiling, require prospective testing and validation. Tissue-based biomarkers such as PD-L1 immunohistochemistry have several limitations due to discordance in assay methodology and trial designs. Novel liquid-biopsy techniques are promising as potential biomarkers. Validated biomarkers that capture the complexity of the biology of both the tumor and the tumor microenvironment are needed in muscle-invasive UCB. Standardization of methods is critical to developing reliable biomarkers to guide clinical management.
- Subjects :
- Oncology
medicine.medical_specialty
DNA repair
Urology
medicine.medical_treatment
030232 urology & nephrology
Antineoplastic Agents
Disease
Malignancy
03 medical and health sciences
0302 clinical medicine
Antineoplastic Agents, Immunological
Internal medicine
medicine
Humans
Neoplasm Invasiveness
Molecular Targeted Therapy
Cisplatin
Tumor microenvironment
Carcinoma, Transitional Cell
Bladder cancer
business.industry
Liquid Biopsy
Muscle, Smooth
Immunotherapy
medicine.disease
Prognosis
Urinary Bladder Neoplasms
030220 oncology & carcinogenesis
Biomarker (medicine)
business
Biomarkers
medicine.drug
Subjects
Details
- ISSN :
- 14338726
- Volume :
- 37
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- World journal of urology
- Accession number :
- edsair.doi.dedup.....b7160593de2503d5731a199d757adbef