A river model to map convergent cancer evolution and guide therapy in RCC Journal Article
| Authors: | Wei, E. Y.; Hsieh, J. J. |
| Article Title: | A river model to map convergent cancer evolution and guide therapy in RCC |
| Abstract: | Intratumoural heterogeneity in clear cell renal cell carcinoma (ccRCC) complicates identification and validation of biomarkers and thwarts attempts to improve precision medicine. Efforts to depict intratumoural heterogeneity and to pinpoint strategies for disease control resulted in the creation of the trunk-branch model of mutational cancer evolution, which emphasizes targeting trunk mutations. However, most patients with ccRCC receiving current therapeutics that target these mutations, such as inhibitors of vascular endothelial growth factors, eventually develop resistance. A novel paradigm might improve depiction of cancer evolution and advise therapeutic selection: the river model is based on findings from multiregion sequencing in samples from exceptional responders to mTOR inhibitors. The accumulating data on genotypic and phenotypic convergence in renal cell carcinoma and other malignancies can be used to examine how a mutable river model might best describe clinically significant phenotype-convergent events that could guide effective cancer control. This model originates from studying exceptional responders and its generalizability awaits validation. © 2015 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | gene mutation; gene sequence; sequence analysis; disease course; review; cancer growth; colorectal cancer; multiple myeloma; breast cancer; genetic variability; gene frequency; kidney carcinoma; carcinogenesis; cancer resistance; cell heterogeneity; genomics; hypoxia inducible factor; metastasis potential; heterozygosity loss; chronic lymphatic leukemia; genetic model; von hippel lindau protein; cancer morphology; molecularly targeted therapy; intratumoral heterogeneity; cancer prognosis; human; priority journal; convergent evolution |
| Journal Title: | Nature Reviews Urology |
| Volume: | 12 |
| Issue: | 12 |
| ISSN: | 1759-4812 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-12-01 |
| Start Page: | 706 |
| End Page: | 712 |
| Language: | English |
| DOI: | 10.1038/nrurol.2015.260 |
| PROVIDER: | scopus |
| PUBMED: | 26526752 |
| DOI/URL: | |
| Notes: | Review -- 1 -- Export Date: 7 January 2016 -- 706 -- Source: Scopus |
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