Genomic heterogeneity in bladder cancer: Challenges and possible solutions to improve outcomes Review
| Authors: | Meeks, J. J.; Al-Ahmadie, H.; Faltas, B. M.; Taylor, J. A. 3rd; Flaig, T. W.; DeGraff, D. J.; Christensen, E.; Woolbright, B. L.; McConkey, D. J.; Dyrskjøt, L. |
| Review Title: | Genomic heterogeneity in bladder cancer: Challenges and possible solutions to improve outcomes |
| Abstract: | Histological and molecular analyses of urothelial carcinoma often reveal intratumoural and intertumoural heterogeneity at the genomic, transcriptional and cellular levels. Despite the clonal initiation of the tumour, progression and metastasis often arise from subclones that can develop naturally or during therapy, resulting in molecular alterations with a heterogeneous distribution. Variant histologies in tumour tissues that have developed distinct morphological characteristics divergent from urothelial carcinoma are extreme examples of tumour heterogeneity. Ultimately, heterogeneity contributes to drug resistance and relapse after therapy, resulting in poor survival outcomes. Mutation profile differences between patients with muscle-invasive and metastatic urothelial cancer (interpatient heterogeneity) probably contribute to variability in response to chemotherapy and immunotherapy as first-line treatments. Heterogeneity can occur on multiple levels and averaging or normalizing these alterations is crucial for clinical trial and drug design to enable appropriate therapeutic targeting. Identification of the extent of heterogeneity might shape the choice of monotherapy or additional combination treatments to target different drivers and genetic events. Identification of the lethal tumour cell clones is required to improve survival of patients with urothelial carcinoma. © 2020, Springer Nature Limited. |
| Keywords: | cancer chemotherapy; cancer survival; treatment outcome; unclassified drug; gene mutation; pathogenesis; review; cancer recurrence; cisplatin; doxorubicin; dose response; systemic therapy; gemcitabine; cancer adjuvant therapy; methotrexate; adenocarcinoma; gene; cancer immunotherapy; gene expression; drug design; bladder cancer; morphology; vinblastine; cancer resistance; transitional cell carcinoma; mutagenesis; genetic heterogeneity; neuroendocrine carcinoma; molecularly targeted therapy; clonal evolution; apolipoprotein b; human; priority journal; checkpoint kinase inhibitor; pembrolizumab; micropapillary urothelial carcinoma; erdafitinib; infigratinib; urogenital tract metastasis; plasmacytoid urothelial carcinoma; apolipoprotein b messenger rna editing enzyme catalytic polypeptide 3; s 1314; apobec3 gene; nested urothelial carcinoma; sarcomatoid urothelial carcinoma |
| Journal Title: | Nature Reviews Urology |
| Volume: | 17 |
| Issue: | 5 |
| ISSN: | 1759-4812 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-05-01 |
| Start Page: | 259 |
| End Page: | 270 |
| Language: | English |
| DOI: | 10.1038/s41585-020-0304-1 |
| PUBMED: | 32235944 |
| PROVIDER: | scopus |
| PMCID: | PMC7968350 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 June 2020 -- Source: Scopus |
