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SUMMARY:Evolutionary cancer therapy
DTSTART;VALUE=DATE-TIME:20180711T052000Z
DTEND;VALUE=DATE-TIME:20180711T054000Z
DTSTAMP;VALUE=DATE-TIME:20210228T005740Z
UID:indico-contribution-445@conferences.maths.unsw.edu.au
DESCRIPTION:Speakers: Alexander Anderson (Moffitt Cancer Center)\nHeteroge
 neity in cancer is increasingly being recognized as a key determinant of t
 umour progression and response to therapy. However\, much of our current u
 nderstanding of this heterogeneity has been driven by our ability to measu
 re it\, and therefore has largely focused on the genomic scale. Ultimately
  such heterogeneity is realized through the generation of distinct phenoty
 pes. In recent years there has been a deeper appreciation for how phenotyp
 ic variation is modulated by a range of biological mechanisms over differe
 nt spatial scales - specifically epigenetic\, metabolic and microenvironme
 ntal. Within a growing tumour\, multiple cellular phenotypes and a spatiot
 emporally-varying microenvironment form a complex ecosystem that exhibits 
 unintuitive\, nonlinear behaviour. \n\nTreatment of advanced cancers has b
 enefited from new agents that supplement or bypass conventional therapies.
  However\, even effective therapies fail as a heterogeneous tumour cell po
 pulation deploys a wide range of resistance strategies. We propose that ev
 olutionary dynamics ultimately determine survival and proliferation of res
 istant cells\, therefore evolutionary treatment strategies should be used 
 with conventional therapies to delay or prevent resistance. Using an agent
 -based framework to model spatial competition among sensitive and resistan
 t populations\, we apply anti-proliferative drug treatments to varying rat
 ios of sensitive and resistant cells. We compare a continuous maximum tole
 rated dose schedule with an adaptive schedule aimed at tumour control thro
 ugh competition between sensitive and resistant cells. We find that contin
 uous treatment cures mostly sensitive tumours\, but with any resistant cel
 ls\, recurrence is inevitable. We identify two adaptive strategies that co
 ntrol heterogeneous tumours: dose modulation controls most tumours with le
 ss drug\, while a more vacation-oriented schedule can control more invasiv
 e tumours.\n\nhttps://conferences.maths.unsw.edu.au/event/2/contributions/
 445/
LOCATION:University of Sydney New Law School/--104
URL:https://conferences.maths.unsw.edu.au/event/2/contributions/445/
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