Lung cancer is the leading cause of cancer-related mortality worldwide. Large-scale sequencing studies have revealed the complex genomic landscape of NSCLC and genomic differences between lung adenocarcinomas (LUAD) and lung squamous cell carcinomas (LUSC). However, in-depth exploration of NSCLC intratumor heterogeneity and cancer genome evolution has been limited to small retrospective cohorts. As such, the clinical significance of ITH and the potential for clonality of driver events to guide therapeutic strategies is not yet defined.

In this talk I will outline how intra-tumor heterogeneity can be deciphered using multi-region sequencing. I will examine how heterogeneity can be utilized to gain a deeper understanding of tumor evolution, focusing on results from the TRACERx  (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study.

I will explore the clinical implications of intra-tumor heterogeneity and consider clinical approaches to tackle this devastating disease. 

Learning Objectives: 

1. Tumour heterogeneity is widespread in early stage NSCLC and occurs at both mutational and copy number level
2. APOBEC-mediate mutagenesis occurs later in lung cancer evolution and is associated with subclonal expansions
3. HLA LOH is a pervasive mechanisms of immune evasion.