OCT 11, 2018 12:00 PM PDT

Lung Cancer Evolution and Immune Escape

Speaker
  • Senior Research Associate, Cancer Genome Evolution Research Group, University College London
    Biography
      Dr. Nicholas McGranahan completed his undergraduate degree in Natural Sciences, specializing in Evolutionary Genetics, at the University of Bath before pursuing post-graduate studies at University College London at the Centre of Mathematics and Physics in the Life Science and Experimental Biology (CoMPLEX). In 2011, Dr. McGranahan joined Professor Charles Swanton's group at the CR-UK London Research Institute (now the Francis Crick Institute), completing a PhD in Cancer Genomics in 2015.

      As a junior group leader and Sir Henry Dale Fellow within the CRUK Lung Cancer Centre of Excellence, Dr. McGranahan's research interests include using bioinformatics to dissect cancer genome evolution and the mechanisms of drug resistance, intra-tumour heterogeneity and genomic instability. His work involves exploring the evolutionary history of cancers through sequencing multiple regions of individual tumours. In particular, Dr. McGranahan's research has focused on understanding the importance of genome doubling in tumour evolution, as well as exploring the mutational processes shaping the genomes of cancers over space and time. Dr McGranahan has authored over 30 articles in high impact journals, including first author publications in New England Journal of Medicine, Science, Nature and Cell.

    Abstract

    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. 


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