L2-Stratifed medicine Flashcards
what is the definition of stratified medicine and biomarker
process of selecting patients for SPECFIC therapies using a BIOMARKER.
biomarker- a measured indicator of a disease process.
what are the features of a good biomarker
> sensitive- high true positive rate > specific- low false positive rate > reproducible > only good/useful for disease being examined > cheap
what are the equations for statistically measuring sensitivity AND specificity of biomarker
sensitivity = true positive (true pos/false negative) specificity = true negative (true neg/false pos)
what methods are used to stratify MOLECULAR GENETICS in cancer? molecular genetics include genetic mutations, gene expression changes and epigenetic modifiers
genetic mutation = DNA seq
change in gene expression = RNA seq
epigentic modifiers = methyl seq, chIP seq
what are the types of biomarkers
> complex - multiple genes
simple - single mutation
predictive - predict response to therapy
prognostic - predicts patients survival chance or disease progression
examples of prognostic and predictive stratifiers
> prognostic - CMS classifier of colorectal cancer –> clusters of patients with same gene expression pattern identified, allows us to understand the broad biology of the tumour to allow prediction of how it will progress
predictive - DDRD stratification assay in breast cancer –> gene expression patterns matched with known in vitro markers of DSB repair = different patient response to chemotherapy for those who had deficient DSB repair
example of an epigenetic biomarker
tumour methylation e.g. OR3A4 methylation in non dysplastic Barett’s = marker of neoplastic progression - PREDICTIVE BIOMARKER
example of an molecularly stratified clinical trial that is in practice
National Matrix Trial - multi-drug, genetic marker directed multi arm Phase II trial in NSCLS - treatement according to molecular phenotype
