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SUMMARY:Deconstructin oncogenesis and tumour suppression to find the best 
 cancer drug targets - Gerard Evan\, Department of Biochemistry\, Unversity
  of Cambridge
DTSTART:20101118T161500Z
DTEND:20101118T180000Z
UID:TALK27471@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Myc and p53 are pleiotropic transcription factors that\, respe
 ctively\, drive and suppress cancer. Myc levels are elevated and deregulat
 ed in most cancers\, suggesting a pivotal role for Myc in oncogenic signal
 ing. De-activation of Myc function in tumours driven by oncogenically acti
 vated Myc triggers their rapid regression through a variety of intracellul
 ar and extracellular mechanisms\, including differentiation\, apoptosis an
 d vascular collapse. However\, Myc mutations are relatively rare and the a
 berrant Myc in most tumours appears to be a consequence of aberrant upstre
 am signals. The extent to which such endogenous Myc\, acting as a client o
 f upstream oncogenes\, is a therapeutic target depends on the degree to wh
 ich it coordinates functions essential for tumour maintenance and what tho
 se functions are\, neither of which is known. To investigate the therapeut
 ic potential of Myc inhibition we have constructed switchable genetic mous
 e models in which endogenous Myc can be systemically and reversibly inhibi
 ted in normal and tumour tissues in vivo. Our data indicate that inhibitin
 g Myc has a remarkably efficacious and durable therapeutic impact on multi
 ple cancer types\, triggering widespread tumour cell apoptosis while elici
 ting only mild\, reversible and non-cytotoxic side effects in normal tissu
 es. The p53 tumor suppressor\, or its attendant pathway\, is functionally 
 inactivated in almost all human cancers. However\, the mechanism by which 
 p53 suppresses tumorigenesis remains obscure. p53 mediates the cellular ap
 optotic and senescence response to DNA damage\, and this is thought to be 
 critical for both tumour suppression and for the progressive erosion of so
 matic regenerative capacity that characterizes aging. However\, using a un
 ique mouse model in which the endogenous p53 gene is replaced by one encod
 ing a ligand-dependent\, reversibly switchable variant of p53\, we show th
 at the p53-mediated DNA damage response is dispensable for tumour suppress
 ion. Hence\, by selectively manipulating the DNA damage and tumour suppres
 sor functions of p53 it may be possible to potentiate tumour suppression a
 nd cancer therapy whilst simultaneously extending life-span. 
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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