A river model to map convergent cancer evolution and guide therapy in RCC

Area of Science:

• Oncology
• Genomics
• Cancer Evolution

Background:

• Intratumoural heterogeneity in clear cell renal cell carcinoma (ccRCC) presents challenges for biomarker discovery and precision medicine.
• Current therapies targeting trunk mutations in ccRCC often lead to acquired resistance.

Purpose of the Study:

• To propose a novel 'river model' paradigm for understanding cancer evolution and guiding therapeutic selection in ccRCC.
• To explore the potential of phenotype-convergent events in guiding cancer control strategies.

Main Methods:

• Analysis of multiregion sequencing data from exceptional responders to mTOR inhibitors.
• Examination of genotypic and phenotypic convergence in renal cell carcinoma and other cancers.

Main Results:

• The river model offers a new perspective on cancer evolution, potentially improving the depiction of clinically significant events.
• Exceptional responders to mTOR inhibitors provide insights into this mutable model.

Conclusions:

• The river model, originating from studies of exceptional responders, may offer a more effective approach to understanding ccRCC evolution.
• Further validation is required to establish the generalizability and clinical utility of the river model.