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SUMMARY:Towards Rational Combination Therapies: Understanding tumor evolut
 ion during therapy response  and resistance - Anna Obenauf\, IMP Vienna
DTSTART:20240418T120000Z
DTEND:20240418T130000Z
UID:TALK209935@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:Targeted therapies and immunotherapies have transformed the cl
 inical care of patients with \nmetastatic cancer. By optimizing treatment 
 with combinations of different therapies\, a cure appears \nwithin reach f
 or many cancers. However\, achieving this goal will require more detailed 
 knowledge of \nthe mechanisms of therapy resistance and immune evasion and
 \, importantly\, of the impact of \ntherapies on tumor evolution\, which m
 ay promote or prevent subsequent therapy responses. The vision \nof my lab
  is to build and exploit this knowledge to identify rational combinations 
 of existing and \nemerging therapies by understanding the complex and dyna
 mic biology of cancer cells and the tumor \nmicroenvironment in all phases
  of therapy. \nRecent work includes the discovery that acquired resistance
  to targeted therapy leads to crossresistance to immunotherapy\, despite 
 their entirely different mode of action (Haas et al.\, 2021\, Nature \nCan
 cer)\, or that resistance to targeted therapy\, including the resistance-c
 onferring mutations and epigenetic mutations are frequently acquired duri
 ng therapy exposure (Umkehrer et al. 2020\, Nature \nBiotechnology). Moreo
 ver\, we have identified novel therapeutic approaches for rare cancers\, s
 uch as \nMerkel cell carcinoma (Leiendecker et al.\, 2020\, EMBO MM) and a
  new oncogenic virus as the cause \nof a human skin cancer (Leiendecker et
  al. 2022\, Cancer Discovery). To break new ground\, a key effort \nin our
  lab is to develop and apply innovative technologies to gain insight into 
 complex response and \nresistance mechanisms in vivo. We\, for example\, r
 ecently developed a functional lineage tracing \napproach termed CaTCH (CR
 ISPRa tracing of clones in heterogeneous cell populations\, Umkehrer et al
 . \n2020\, Nature Biotechnology)\, which allows to trace clones through ev
 olutionary bottlenecks\, but also \nallows to “go back in time” to ret
 rospectively isolate founding clones from millions of cells prior to \nevo
 lutionary selection. Thus\, CaTCH has the potential to give unprecedented 
 insights into tumor \nevolution and we are applying it to decipher mechani
 sms underlying therapy resistance\, metastasis \nand immune evasion. \nIn 
 my talk I will focus on our newest discoveries providing a mechanistic und
 erstanding of how cancer \ncells orchestrate an immune-evasive TME and dis
 cussrational combination therapies that could extend \nthe benefit of immu
 notherapy to a larger number of patients
LOCATION:CRUK CI Lecture Theatre
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