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SUMMARY:Industry Insights Seminar - Novartis - Targeting the WRN helicase 
 in MSI cancers - Dr Marta Cortes-Cros (Novartis)
DTSTART;VALUE=DATE-TIME:20250612T120000
DTEND;VALUE=DATE-TIME:20250612T130000
UID:https://new.talks.ox.ac.uk/talks/id/e7ba7596-1cca-4ab4-b309-cd3cacef0a
 e8/
DESCRIPTION:The RecQ DNA helicase WRN was identified as a synthetic lethal
  target in MSIhigh tumors by several genetic screens. Despite recent advan
 ces in the treatment of MSIhigh tumors by immune checkpoint inhibitors\, a
  significant proportion of patients still fails to respond to or relapses 
 after single agent anti-PD1 or combination of anti-PD1 plus anti-CTLA4 tre
 atments. We will present the biochemical\, cellular and pharmacological ch
 aracterization of the first potent and selective WRN helicase inhibitor\, 
 HRO761. We will show that HRO761 is an allosteric WRN inhibitor that binds
  at the interface of the D1 and D2 helicase domains\, thus locking WRN in 
 an inactive conformation. We will further show that pharmacological inhibi
 tion of WRN by HRO761 recapitulates the phenotype observed by WRN genetic 
 suppression\, leading to activation of the DNA damage response and inhibit
 ion of tumor cell growth selectively in MSIhigh but not in MSS cells. In a
 ddition\, we will show that WRN inhibition leads to WRN protein degradatio
 n only in MSIhigh tumor cells and give insights into the mechanism of WRN 
 degradation upon DNA damage response induction. A phase 1 clinical trial w
 ith HRO761 is currently ongoing to assess the safety\, tolerability and pr
 eliminary anti-tumor activity in patients with MSIhigh colorectal cancer a
 nd other MSIhigh solid tumors\nSpeakers:\nDr Marta Cortes-Cros (Novartis)
LOCATION:IMS-Tetsuya Nakamura Building (Ground Floor Seminar Room)\, Roose
 velt Dr\, Headington OX3 7TY
TZID:Europe/London
URL:https://new.talks.ox.ac.uk/talks/id/e7ba7596-1cca-4ab4-b309-cd3cacef0a
 e8/
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DESCRIPTION:Talk:Industry Insights Seminar - Novartis - Targeting the WRN 
 helicase in MSI cancers - Dr Marta Cortes-Cros (Novartis)
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