Model systems

jambomber's version from 2015-05-22 14:17

Section 1

Question Answer
What do we use model systems for?Determining the efficacy toxity and pharmokinetics of a drug
What percentage of clinal trails for novel drg candidates fail @ first hurdle85%
What is a problem with model systemsCannot mimic human TME, angiogenesis maintainance or progression
What differences exist between humans and models. Give an examplGenentic immunological and cellular differences. TF binding sites differ in more than 50% of cases
What is an example of a disastorous trailTGN 1412 Agonistic anitCD28 immnuological treament leads to catstrophic organ failur
What is n example of useless promising candidateHh Agonisists have no effect comp to placebo in phase 2
what would you say about the power of animal models for clinical effieincyIt is a matter of debate
What is a major problem with methodology?Not sma erigour as clinical. Confounding factors such as stress influence
Led to:CML gleevec, HPV vaccine
What else do we use models for?Examine the contribution of a molecular process to cancer in order todev more effective treatments
Define a driver mutationCausally implicated in tumourigenisis Initaion, Engine = tumour maintenance
What does studying mutations in melanoma show?Very few mutations observed correlate with disease- most = Synonomous
How related are humans to most modles30%
What has Drosophila prodived model forMultiple endocrine neoplasia

Section 2

Question Answer
how many papers did Amgen investigate 53 only 11
What was unique about reproducible experimentsRigorous slection of reagants and controls for investagator bias
What study is AMGEN consistent withBayer Healthcare 25% of preclinical studies are abs rubbish
What do the authors reccomendEqual wieghting to negative results, Less emphasis on impact of publications in driving career advancement
What is a major difficulty in cancerPutcome measured as long term patient survival- many years before applicabilty determined
why such a high failure rateInadequate models , diseases is complex and fundamental problems exist int eh way reasearch is conducted/
How many drugs FDA approved68
What makes PDX so great?Physiological relevant oxygen and hormone levels. can be orthotopic- mimic native envirnment
What are some problems w/ PDX Variable engraftment frequency- could not est breast cancer model 4 a long time , lose stroma and lymphocytes after first passahe , Takes uo to 24 weeks for tumour to arise
What is great anout PDX 2)Faithful to cellular architecture of tumor natural state
What drugs have PDX lead to?Improved understanding of angiogenesis and drugs such as Bevacuzimab

Section 3