Cancer evolution through space and time - Prof Charles Swanton - UCL LHL

About this video

• Video Title: Cancer evolution through space and time - Prof Charles Swanton - UCL LHL
• Channel: UCL Lunch Hour Lectures
• Speakers: Professor Charlie Swanton
• Duration: 00:39:01

Overview

Professor Charles Swanton discusses cancer evolution, emphasizing that cancers evolve in a branched, rather than linear, manner. He explains how this genetic diversity within tumors leads to drug resistance and treatment failure, and highlights the importance of understanding this evolution to develop more effective therapies, particularly in lung cancer.

Key takeaways

• Cancer Evolution is Branched, Not Linear: Tumors evolve through a process of branched evolution, with multiple subclones arising from a common "trunk" of mutations. This contradicts the older model of linear evolution where mutations occur sequentially.
• Genetic Diversity Drives Drug Resistance: The inherent genetic heterogeneity within a tumor means that a single biopsy may not represent the entire tumor's genetic landscape. This diversity leads to varied responses to treatment, with some subclones developing resistance to therapies while others do not.
• Trunk vs. Branch Mutations: Mutations can be categorized as "trunk" (present in all cells, occurring early) or "branch" (present in specific subclones, occurring later). Targeting trunk mutations is crucial for effective treatment, as resistance often emerges from these later branch mutations.
• Chromosomal Instability is Key to Outcome: While micro-evolution (point mutations) is common, chromosomal instability, including genome doubling events, appears to be a stronger predictor of patient outcome in lung cancer, suggesting that large-scale genetic changes drive aggressive disease.
• New Therapeutic Strategies Needed: Traditional treatments targeting single mutations are insufficient due to tumor evolution. Future strategies should aim to target multiple trunk alterations simultaneously, potentially by leveraging the immune system or developing combination therapies with high specificity.