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SUMMARY:Mapping phospho-catalytic dependencies of therapy-resistant tumors
  reveals new actionable vulnerabilities
DTSTART:20191218T120000
DTEND:20191218T130000
DTSTAMP:20260404T045554Z
UID:5f524b0892816a40e5fd0cf51c403c30257befa00ed494463a556baf
CATEGORIES:Conferences - Seminars
DESCRIPTION:Dr. Jean-Philippe Coppé\, Research Scientist Helen Diller Fam
 ily Comprehensive Cancer Center\, Department of Laboratory Medicine Univer
 sity of California San Francisco\nA key to successful therapy is the ident
 ification of critical aberrant signaling networks whose inhibition would r
 esult in system failure of diseased cells. We have developed an innovative
  biotechnology pipeline to explore kinase-signaling networks in cell model
 s and patient tissues. This high throughput kinase-activity mapping (HT-KA
 M) system uses peptide libraries as combinatorial sensors to reveal the id
 entity and activity of kinases. This versatile strategy provides access to
  a vastly unexplored yet highly valuable molecular parameter with consider
 able potential to innovate the discovery of actionable kinase enzymes for 
 precision medicine. After providing examples of newly found cooperative me
 chanisms of therapeutic resistance in BRCAdeficient triple-negative breast
  cancer and in BRAFV600E melanoma and colorectal tumors that lead us to de
 sign new and more effective combinatorial targeted therapy treatments tran
 slatable in patients\, I will discuss how the systematic mapping of phosph
 o-catalytic circuits could help identify druggable dependencies that drive
  immunoevasion of persistent senescent cells in chemotherapy-resilient tum
 ors or in dysfunctional aging tissues.\nA key to successful therapy is the
  identification of critical aberrant signaling networks whose inhibition w
 ould result in system failure of diseased cells. We have developed an inno
 vative biotechnology pipeline to explore kinase-signaling networks in cell
  models and patient tissues. This high throughput kinase-activity mapping 
 (HT-KAM) system uses peptide libraries as combinatorial sensors to reveal 
 the identity and activity of kinases. This versatile strategy provides acc
 ess to a vastly unexplored yet highly valuable molecular parameter with co
 nsiderable potential to innovate the discovery of actionable kinase enzyme
 s for precision medicine. After providing examples of newly found cooperat
 ive mechanisms of therapeutic resistance in BRCAdeficient triple-negative 
 breast cancer and in BRAFV600E melanoma and colorectal tumors that lead us
  to design new and more effective combinatorial targeted therapy treatment
 s translatable in patients\, I will discuss how the systematic mapping of 
 phospho-catalytic circuits could help identify druggable dependencies that
  drive immunoevasion of persistent senescent cells in chemotherapy-resilie
 nt tumors or in dysfunctional aging tissues.\nA key to successful therapy 
 is the identification of critical aberrant signaling networks whose inhibi
 tion would result in system failure of diseased cells. We have developed a
 n innovative biotechnology pipeline to explore kinase-signaling networks i
 n cell models and patient tissues. This high throughput kinase-activity ma
 pping (HT-KAM) system uses peptide libraries as combinatorial sensors to r
 eveal the identity and activity of kinases. This versatile strategy provid
 es access to a vastly unexplored yet highly valuable molecular parameter w
 ith considerable potential to innovate the discovery of actionable kinase 
 enzymes for precision medicine. After providing examples of newly found co
 operative mechanisms of therapeutic resistance in BRCAdeficient triple-neg
 ative breast cancer and in BRAFV600E melanoma and colorectal tumors that l
 ead us to design new and more effective combinatorial targeted therapy tre
 atments translatable in patients\, I will discuss how the systematic mappi
 ng of phospho-catalytic circuits could help identify druggable dependencie
 s that drive immunoevasion of persistent senescent cells in chemotherapy-r
 esilient tumors or in dysfunctional aging tissues.\n\nSELECTED REFERENCES\
 n\n	Olow A#\, Chen Z#\, Niedner RH\, Wolf DM\, Yau C Pankov A\, Lee ‎EPR
 \, Brown-Swigart L\, van ‘t Veer LJ\, Coppé JP. An atlas of the human k
 inome reveals the mutational landscape underlying dysregulated phosphoryla
 tion cascades in cancer. (2016) Cancer Research 76(7): 1733-45. PMID: 2692
 1330\n	Coppé JP *\, Mori M\, Pan B\, Yau C\, Wolf DM\, Ruiz-Saenz A\, Bru
 nen D\, Prahallad A\, Cornelissen-Steijger P\, Kemper K\, Posch C\, Wang C
 \, Dreyer CA\, Krijgsman O\, Lee PRE\, Chen Z\, Peeper DS\, Moasser MM\, B
 ernards R\, van ‘t Veer LJ. Mapping phospho-catalytic dependencies of th
 erapy-resistant tumors reveals actionable vulnerabilities. (2019) Nature C
 ell Biology. 21(6): 778-790. PMID: 31160710    * corresponding author\n
 	Muñoz DP#\, Yannone SM#\, Daemen A\, Yu Sun Y\, Vakar-Lopez F\, Kawahara
  M\, Freund AM\, Rodier F\, Wu JD\, Desprez PY\, Raulet DH\, Nelson PS\, v
 an ’t Veer LJ\, Campisi J\, Coppé JP. Targetable mechanisms driving imm
 unoevasion of persistent senescent cells link chemotherapy-resistant cance
 rs to aging. (2019) Journal of Clinical Investigation insight. 4(14): e124
 76. PMID: 31184599\n	Atreya CE and Coppé JP (co-PIs). Kinome-guided targe
 ting of cooperative dependencies in BRAF and KRAS mutated colorectal cance
 r. 06/01/2019 – 05/30/2025. NIH/NCI R01 CA229447-01\n\n\n 
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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