Lecture 6 - Biomarkers Flashcards
What is a tumour profile?
Unique combination of DNA changes of a tumour
Examples of proto-oncogenes
growth factors • growth factor receptors • signal transduction proteins (RAS) • nuclear regulatory proteins • cell cycle regulators
Which cancer is caused by EGFR (ERB2) overexpression?
Squamous cell lung carcinomas
Gliomas
KIT point mutation
Gastrointestinal stromal tumors
and other soft tissue tumors
Kras point mutation 3
Colon carcinoma
Lung carcinoma
pancreatic carcinoma
ABL translocation
CML and ALL
Braf point mutation
Melanomas, Hairy cell
laeukemia
Nuclear reg proteins examples
c-myc, n-myc, lmyc
What are driver mutations?
mutations involved in
development or progression of a tumour:
“actionable” drivers:
have significant
diagnostic, prognostic, or therapeutic implications in subsets of
cancer patients and for specific therapies
What are passenger mutations indicative of?
indicative of a high mutation rate
resulting from carcinogens and DNA instability.
What does the identification of biomarkers during anti cancer drug development lead to?
Increases chances of success
Accelerated drug approval process by providing effective patient stratification strategies in clinical trials
Two types of biomarkers
Prognostic and predictive
What do prognostic biomarkers give information about?
Disease outcome independent of treatment - or positive or negative for a mutation can be indicative of positive or poor prognosis
What do predictive biomarkers give information about?
Disease outcome related to a treatment. I.e. Positive or negative for a mutation predicts response to a treatment.
Two major types of NSCLC
Adenocarcinoma sand squamous cell carcinoma
Adenocarcinoma characteristics
Arise in more distal airways
Have glandular histology
Express TTF1 and CK7
Squamous carcinoma characteristics
Arise in more proximal airways
Squamous differentiation
Express ck 5/6, sox2, and p63
2 biomarkers used in lung cancer
EGFR
ALK
Two EGFR Inhibitors:
Gefitinib and erlotinib
ALK mutation
Gene rearrangement in the EML4 gene and ALK GENE leads to constitutive activation of ALK in NSCLC
How many percent of patients have EML4/ALK mutations?
4-5%
Who are EGFR mutations seen in?
Women and non smokers
Who are EML4/ALK mutations seen in?
Young people, non or light smokers with adenocarcinoma
