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SUMMARY:Cancer evolution\, immune evasion and metastasis - Professor Charl
 es Swanton FRCP FMedSci FAACR FRS
DTSTART:20210309T180000Z
DTEND:20210309T193000Z
UID:TALK157465@talks.cam.ac.uk
CONTACT:92260
DESCRIPTION:This talk is open to all regardless of membership.\nRegister h
 ere: https://forms.gle/tx8aifBNdXSV7H7T9\n\nAbstract:\n\nEvidence supports
  complex subclonal relationships in solid tumours\, manifested as intratum
 our heterogeneity. Parallel evolution of subclones\, with distinct somatic
  events occurring in the same gene\, signal transduction pathway or protei
 n complex\, suggests constraints to tumour evolution that might be therape
 utically exploitable. Data from TRACERx\, a longitudinal lung cancer evolu
 tion study will be presented. Drivers of tumour heterogeneity change durin
 g the disease course and contribute to the temporally distinct origins of 
 lung cancer driver events. APOBEC driven mutagenesis appears to be enriche
 d in subclones in multiple tumour types. Oncogene\, tumour suppressor gene
  and drug induced DNA replication stress are found to drive APOBEC mutagen
 esis. Phylogenetic tracking detects minimal residual disease and clonal ev
 olution of disease from primary to metastatic sites\, presenting opportuni
 ties for drug development.\nOn-going chromosomal instability\, manifested 
 as Mirrored Subclonal Allelic Imbalance (MSAI) is found to be a major driv
 er of intratumour heterogeneity across cancer types\, contributing to para
 llel evolution and selection. Subclonal driver events\, evidence of ongoin
 g selection within subclones\, combined with genome instability driving ce
 ll-to-cell variation is likely to limit the efficacy of targeted monothera
 pies\, suggesting a need for new approaches to drug development and integr
 ation of cancer immunotherapeutic approaches. Multiple adaptive mechanisms
  to neo-antigen evolution have been found in TRACERx highlighting cancer c
 hromosomal instability driving immune evasion and HLA loss and loss of clo
 nal neoantigens as well as epigenetic repression of neo-antigens. The clon
 al neo-antigenic architecture may act as a tumour vulnerability to mitigat
 e resistance and treatment failure.\n\nSpeaker Profile:\n\nProfessor Charl
 es Swanton completed his MD-PhD training in 1999 at the Imperial Cancer Re
 search Fund Laboratories and Cancer Research UK clinician scientist/medica
 l oncology training in 2008. Prof Swanton is a Senior Group Leader of the 
 Cancer Evolution and Genome Instability Laboratory at the Francis Crick In
 stitute and combines his research with clinical duties at UCLH\, as a thor
 acic oncologist\, focused on how tumours evolve over space and time. Prof 
 Swanton is the Chief Investigator of TRACERx\, a lung cancer evolutionary 
 study and the national PEACE autopsy program. Prof Swanton was appointed F
 ellow of the Academy of Medical Sciences in 2015\, awarded the Napier Prof
 essor in Cancer by the Royal Society in 2016\, appointed Cancer Research U
 K’s Chief Clinician in 2017\, and elected Fellow of the Royal Society in
  2018 and Fellow of the Academy of American Association for Cancer Researc
 h in 2020. In 2016\, he co-founded Achilles Therapeutics\, a UCL/CRUK/Fran
 cis Crick Institute spin-out company\, assessing the efficacy of T cells t
 argeting clonal neoantigens. Most recently\, Prof Swanton was awarded the 
 ESMO Award for Translational Cancer Research (2019) and the Addario Lung C
 ancer Foundation Award and Lectureship at the International Lung Cancer Co
 ngress (July 2020).
LOCATION:Google Meets
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