Cancer Biomarkers Flashcards
What is a cancer biomarker?
A substance or process that is indicative of the presence of cancer in the body
What 3 primary ways are biomarkers used in cancer research and medicine?
- Prognostic
- Diagnostic
- Predictive (response to treatment)
What other uses do cancer biomarkers have?
- Monitoring a condition
- Risk/screening
What 4 categories of biomolecules can be used as biomarkers?
- Genetic
- Epigenetic
- Proteomic
- Glycomic
What genetic biomolecules can be used as biomarkers?
- DNA mutations/CNA (circulating nucleic acids)
- mRNA expression
What epigenetic biomolecules can be used as biomarkers?
- DNA methylation
- Histone methylation
- miRNA gene silencing
What proteomic biomolecules can be used as biomarkers?
- Protein levels
- Post translational modifications
What glycomic biomolecule can be used as biomarkers?
-Glucose metabolism
What is genomics?
Mutation and gene expression profiling
What is transcriptomics?
All RNA transcripts
What is proteomics?
Proteome profiling of biological fluids
What is metabolomics?
Metabolic fingerprinting in biological systems
What is lipidomics?
Complete lipid profile within a cell, tissue or organism
What is epigenetics?
Modification of nuclear DNA
What can be looked for in the blood?
- Circulating tumour cells (CTCs)
- DNA/RNA
- miRNA
- PSA
- Exosomes
What can be looked for in tissues?
- DNA/RNA
- AMACR
- Histopathology/IHC
- Gleason score
What can be looked for in urine?
- DNA/RNA
- miRNA
- Prostasomes/Exosomes
- PCA3
- TMPRSS2:ERG
What are AMACR, TMPRSS2:ERG and PCA3?
Prostate cancer markers
What can be looked for in semen?
- Prostasomes
- Exosomes
- Proetins
- DNA/RNA
What are the advantages of blood/plasma biomarkers?
The procedure is minimally invasive and low cost
What are the disadvantages of blood/plasma biomarkers?
Complex, and wide patient variability
What are the advantages of tissue biomarkers?
Diagnostic and prognostic, and can analyse markers directly from tissue
What are the disadvantages of tissue biomarkers?
Highly invasive, high cost, and associated side effects due to method of acquiring sample
What are the advantages of urine biomarkers?
Non invasive, large volume, low cost, get access to proteins directly from prostate
What are the disadvantages of urine biomarkers?
Low concentration of molecules, high variability between patients
What are the advantages of semen biomarkers?
relatively non invasive, large volume, low cost, access to proteins directly from prostate
What are the disadvantages of semen biomarkers?
Low concentration of molecules, high variability between patients
What 7 things should the ideal biomarker be?
- Specific
- Sensitive
- Predictive
- Robust
- Reflective of kinetics
- Minimally-invasive to obtain
- Have (pre-)clinical importance
What should a biomarker be specific to?
Disease type and stage
What should a biomarker be sensitive to?
Single molecules - detections at earliest stage for optimised treatment
What should a biomarker be predictive of?
- Stratification
- Treatment response
- Recurrence
How should a biomarker be robust?
Fast, simple and cheap to test for
What kinetics should a biomarker reflect?
Pathological processes and therapy response
What are genetic biomarkers of risk?
Method for determining predisposition and risk of developing cancer.
What is the genetic biomarker of risk for breast cancer and ovarian cancer?
BRCA1/2
What is a genetic biomarker of cancer risk that works for brain cancer, cervical cancer and oral cancer?
Abnormal methylation/hypermethylation of specific genes
What mutations are genetic biomarkers of risk for GI cancers?
EGFR, KRAS, TP53 and ERBB2
What qualities must biomarkers for cancer SCREENING have?
- Highly specific to minimise false positives and negatives
- Detetable with minimal complication/cost
- Released into serum or urine for minimal invasiveness
- Clearly reflect the different early stages of disease
What is PSA produced by?
Epithelial cells of the prostate
How is PSA present in healthy males?
At small quantities
How does this change in males with prostate cancer?
Elevated in some patients
What levels of PSA are considered suspicious and require biopsy?
4-10ng/ml
Is PSA level specific enough?
Not considered to be in UK so not part of screening programme for prostate cancer (UK doesn’t have one)
What is PSA used with in risk stratification of prostate cancer?
Grade (Gleason grading) and Stage (imaging)
What is the low risk score for prostate cancer risk stratification?
Psa <10, Gleason score ≤6, and Clinical stage ≤T2a
What is the intermediate risk score for prostate cancer risk stratification?
PSA 10-20, Gleason score 7, or clinical stage T2b/c
What is the high risk score for prostate cancer risk stratification?
PSA >20, Gleason score ≥8, or clinical stage ≥T3
How are cervical cells collected?
Pap smear
Who is the cervical screening programme available to?
Women aged 25 to 64
How often are women invited to be screened for cervical cancer?
25-49 every 3 years, 50-64 every 5 years
What is the diagnostic biomarker for liver cancer?
Alpha-foetoprotein
What is the diagnostic biomarker for ovarian cancer?
Cancer antigen 125 (aka MUC16) - not foolproof
What is the diagnostic biomarker for breast cancer in metastatic disease?
CA15-3
What is the diagnostic biomarker for colorectal cancer?
CA19-9
What is the diagnostic biomarker for pancreatic cancer?
CEA (Carcinoembryonic Antigen)
What is the diagnostic biomarker for prostate cancer?
PSA
What is the diagnostic biomarker for chronic myeloid leukaemia?
BCR-ABL - very commonly used as 95% of CML patients have it
What is BCR-ABL in CML targetted by?
Imatinib
What is a prognostic biomarker?
Biomarker that indicates the likely course of disease in an untreated individual
What is a predictive biomarker?
Biomarker that identifies subgroups of patients who are most likely to respond to a given therapy
What is a predictive biomarker in highly aggressive breast cancers?
ERBB2 amplification
What is ERBB2 amplification positive breast cancer targetted by?
Trastuzumab (herceptin)
Why are circulating biomarkers so important?
Tumours vary person to person, but the tumour within one patient can also be different to itself - Heterogeneity.
What is cell-free DNA?
DNA circulating in plasma, derived by apoptosis/necrosis/active secretion.
When is cell-free DNA elevated?
In tumour cell turnover
What can cfDNA be used as an early diagnostic marker in?
Breast cancer detection - analyse in patients with suspicious mammogram.
What are CTCs?
Circulating tumour cells - tumour cells that have been shed into the bloodstream
What are CTCs useful for?
Prognosis and prediction, as well as being very useful in monitoring.
How many CTCs is bad?
> 5 CTCs in one sample = very bad prognosis
What are the problems with CTCs?
They are very rare (1:1,000,000) and difficult to isolate
Where are circulating miRNAs used?
In the USA as a biomarker. Not the UK as too variable.
