Details

Autor(en) / Beteiligte

• Soultati, Aspasia
• Stares, Mark
• Swanton, Charles
• Larkin, James
• Turajlic, Samra

Titel

How should clinicians address intratumour heterogeneity in clear cell renal cell carcinoma?

Ist Teil von

• Current opinion in urology, 2015-09, Vol.25 (5), p.358-366

Ort / Verlag

United States: Copyright Wolters Kluwer Health, Inc. All rights reserved

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• PURPOSE OF REVIEWDespite the availability of multiple targeted therapies, the 5-year survival rate of patients with metastatic clear cell renal cell carcinoma (ccRCC) rarely exceeds 10%. Recent insights into the mutational landscape and evolutionary dynamics of ccRCC have offered up a plausible explanation for these outcomes. The purpose of this review is to link the research findings to potential changes in clinical practice. RECENT FINDINGSIntratumour heterogeneity (ITH) dominates the evolutionary landscape in ccRCC at the genetic, transcriptomic and proteomic level. Spatial and temporal separation of tumour subclones within the primary tumour as well as between primary and metastatic sites has been demonstrated at single nucleotide resolution. In the cases analysed to date, approximately two-thirds of somatic mutations are not shared between multiple biopsies from the same primary tumour. Very few of the key disease-driving events are shared across all primary tumour regions (with the exception of VHL and loss of chromosome 3p), whereas the majority are restricted to one or more tumour regions (TP53, SETD2, BAP1, PTEN, mTOR, PIK3CA and KDM5C). SUMMARYITH must be considered in the management of ccRCC with respect to diagnostic procedures, prognostic and predictive biomarkers and drug development.