7) Biomarkers Flashcards
What is a cancer biomarker?
A substance or process that is indicative of the presence of cancer in the body
What are the uses of cancer biomarkers?
Diagnosis, prognosis, predictive (how well a patient will respond to treatment
What are some different types of biomarkers? (broad)
Genetic - DNA mutations, mRNA expression
Epigenetic - DNA methylation
Proteomic - protein levels
Glycomic - glucose metabolism
What molecular markers can be obtained from tissues of the body?
DNA, RNA, protein, miRNA and mRNA
What are some sources of biomarkers?
Blood, tissue, urine, semen
What are features of the ideal biomarker?
Specific, sensitive (detection at early stage), predictive, robust, minimally invasive, reflect kinetics (e.g. tumour size increases, biomarker level increases)
Give examples of genetic biomarkers for risk:
Mutation in EGFR
BRCA1/2
Abnormal methylation of tumour suppressor genes
How can prostate specific antigen be used as a biomarker?
It is elevated in some patients with prostate cancer so can be used for detection
Combined with grade and stage for risk stratification
How is HPV used as a biomarker?
Pap smear for HPV detection and HPV used a risk predictor
What is a diagnostic biomarker in liver cancer?
Alpha-fetoprotein
What is a diagnostic biomarker in ovarian cancer?
Cancer antigen 125
What is a diagnostic biomarker in colorectal cancer?
Carbohydrate antigen 19-9
What is a diagnostic biomarker in pancreatic cancer?
Carcinoembryonic antigen (CEA)
What is a biomarker in metastatic breast cancer?
CA15-3, tracks progress
Give an example of genetic diagnostic biomarker of cancer:
BCR-ABL translocation (Philadelphia chromosome) in CML
What is a prognostic biomarker?
Indicates the likely course of the disease in an untreated individual
What is a predictive biomarker?
Identifies subpopulations of patients who are most likely to respond to a given therapy
Give examples of prognostic biomarkers:
TIMP1 in multiple myeloma
Oestrogen receptor in breast cancer
Why are predictive biomarkers needed?
Reduces the unnecessary treatment and adverse effects
Can quickly highlight acquired resistance to therapy
Give examples of predictive biomarkers:
HER2 amplicfication, targeted by trastuzumab
EGFR mutation, response to erlotinib in non-small cell lung cancer
BRAF mutation, response to vemurafenib in metastatic melanoma
What is tumour heterogeneity?
Different regions in the tumour show different mutations
Why are liquid biopsies advantageous?
Give a more representative sample of all the clones in the tumour and is minimally invasive
What are some examples of biomarkers from liquid biopsy?
Circulating tumour cells
Cell free DNA
Exosomes - tiny vesicles shed form cells, giving info about DNA
What is cell free DNA?
Derived from apoptosis, necrosis or active secretion and elevated in tumour cell turnover. Shows mutations, copy number variants and methylation
How can cfDNA act as a diagnostic biomarker?
Can show mutations that the tumour has gained, also helps with prognosis
How can cfDNA act as a predictive biomarker?
Shows mutations that the tumour has causing resistance to therapy
Also shows gene amplified that can cause relapse
What are circulating tumour cells?
CTCs shed into bloodstream (rare), can be prognostic and predictive and used in monitoring
How can circulating tumour cells be used as biomarkers?
Isolated and sequenced, tested and cultured to give information about mutations used for prognosis and predictions
How can circulating miRNAs be used as biomarkers?
Regulate gene expression so can be used in diagnosis, prognosis and predictive
