Companion Diagnostics Flashcards
Why is treatment success so low?
Patients respond differently
disease develops resistance
What is TI ratio?
Ratio of effective dose to toxic dose
What are biologics?
new drugs based on cell or animal products eg mAb, genetic therapies
What is a companion diagnostic?
Device which is essential for the safe & effective use of a corresponding medicinal product
What do companion diagnostics identify?
Pts who are most likely to benefit from therapy
Pts most likely to be at increased risk for serious adverse reactions due to treatment
What is theranostics?
Combining diagnosis & targeting appropriate therapy
What is the difference between CDXs & complementary diagnostics?
CDx - connected to a specfici drug
Complementary - associated more broadly with an entire class of drugs
What is the MoA of nivolumab?
PD-L1blocker - inhibits immune evasion of tumour cells
What is a pharmacological profile?
Determine acute toxicity of the drug in cell/organoid model
What are 5 different types of clinical trails?
Treatment
Prevention
Diagnostic
Screening
QoL
What is the purpose of phase I?
Test drug in a small group to evaluate safety
What ios the purpose of phase II/
Larger group to test efficacy & further test safety
What is the purpose of phase III?
Large groups to confirm efficacy, compare to common treatments, S/Es
What is the purpose of phase IV?
Effectiveness in public
What cohort is companion dx used?
Select people that have target & are most likely to respond to treatment
What are 2 types of trials?
Umbrella - impact of different drugs on different mutations in one cancer type
Basket - effect of one or more drugs on one or more mutations in a variety of cancers
What are 3 Companion Dx product services?
Kits for lab customers
Lab-developed tests
Analyte specific reagents
What can we look at by measuring cytochrome P450 enzymes?
Class of proteins to metabolise drugs
Fast/slow metaboliser = more/less of drug
Cannot metabolise than should not receive drug
How does CYP2D6 metabolism affect codeine treatment?
Increased CYP2D6 function = need high morphine administration
What was the first predictive biomarker used for cancer?
ER testing by tissue IHC (Cdx) to identify individuals with BCa for tamoxifen treatment
What is the MoA of tamoxifen?
Competes with endogenous oestrogens for ER in cytosol –> lowers transcription of oestrogen-responsive genes
What is Herceptin used for?
BC overexpressing HER2
What is HER2 +ve BC?
Constitutively on growth factor signalling - cancer proliferation
What type of mAB is trastuzumab?
Humanised murine monoclonal antibody
What is the MoA of Trastuzumab?
Binds to HER2/ERBB2 -> blocks signaling, triggers immune response, HER2 dimers endocytosised
What family is the human EGFR2 part of?
Wider family of receptors with intergral tyrosine kinase activity
What drug is trastuzumab given with?
Taxane
What is the CDx test for HER2?
Immunostaining (subjective scale)
FISH (more accurate)
What do oncologia’s device (Oncofocus) look at?
Test for all types of 505 DNA/RNA tumour gene variants
What gene variants does Oncofocus look at?
CNV
gene fusions
oncogene
TSG mutations
deletions
What is polyneuropathy caused by?
hereditary transthyretin mediated amyloidosis
What is the Cdx for haTTR?
TTR gene mutation analysis
What % of trials are using Cdxs?
50%
