WEEK 2 - Cancer screening and detection/biomarkers Flashcards
(18 cards)
Provide basic understanding of “cancer screening and detection”
What is cancer screening and its AIM
Use of sumple tests to identify pre-clinical disease that may not be recognsied by Health Care service
AIM: reduce mortality and improve QoL
What impacts the “validity of screening”
Validity is impacted by 2 factors: Sensitivity and Specificity
Sensitivity = how good the test is at finding people who actually have the disease.
- i.e. High sensitivity = few cases missed
Specificity = how good the test is at saying people don’t have the disease when they really don’t
- i.e High specificity = few false alarm
What impacts the “validity of the program”
- That pts in the target population are identified + attend
- Have adequate facilities for test to be taken
- Adequate facilities for diagnostic confirmation
- Carefully designed referal systems in palce
Explain the 4 biases in cancer screening
- Healthy Volunteer Bias
- people who go for screening are often healthier overall
- makes screening look more effective than it really is
- e.g. welathier, more educated, healthier lifestyle habits = may live longerregardless of screening - Lead-time Bias
- Lead time = time between screen detected (asymptomatic) and symptom-detected diagnosis
- AIM of screening is to diagnose cancer earlier BUT doesn’t always mean people live longer
- Peopl are just aware of the cancer sooner / for longer time - Length-Biased Sampling
- time between detection of asymptomatic cancer + when symptoms start occuring
- Screening is more likely to catchslow-growing cancers, which naturally have better outcomes - Overdiagnosis (2 scenarios)
1. Cancer is so benign that it virtually has no growth potential / grows very slow
2. Cancer grows so slow it wouldn’t cause symptoms i.e pt would die from something else first
List the 3 Cancer screening methods
Each method has examples within them
- Imaging Techniques
- e.g. CT, MRI, Ultra sound and PET scans
- Histological Examinations
- biopsy and tissue analysis (invasive)
- Can detect if have specific proteins in cancer cells vs non-cancerous
- Molecular Diagnostics
- blood and liquid biopsies
- take blood sample from patient + detect diff. proteins present in high conc. = things released by cancer cells
- Detect CTCs, ctDNA, cfDNA
Example: Cervical, Bowel and Breast screening
What is CTCs
CTCs = circulating tumour cells
- CTCs shed into bloodstream from primary or metastatic sites
- normal cells dont have ability to get through blood vessel wall + enter stream - Shed cells are transported via cirulcation to other organs (= metastasis)
- CTCs are significant in mamangement of MC
- guides treatment, response, prognsois, recurrence etc.
MC = metastatic cancer
What is ctDNA / cfDNA
Both are biomakers
ctDNA = circulating tumour DNA
- Released by cancer cells into circulation
- a free DNA molecules
cfDNA = circulating cell free DNA
- a free DNA molecule released by dead tumour cells (that enetered bloodstream)
- found in plasma of cancer pts
NOTE: both can be used for:
- EARLY detection of cancer
- Guiding treatment
- Monitoring drug resistance
- Monitoring resposne
What are cancer biomarkers and its use
Biological molecules found in blood, bodily fluids or tissues
- specific to cancer cell
- signs of abnromal processes, condition or disease
USE of biomakrers:
- Detect early-stage cancer
- Influence diagnsois, prognosis
- Relapse monitoring
- Improve pt survival and QoL
- can tailor treatment
What 3 characteristics must be present for a molecule to be classed as a cancer biomarker
- Expressed only by cancer cells
= marker can be targetted - Expressed in different levels to normal cells
- e.g. high expression in cancer + low expression in normal cells
- Alterled level of marker expression has an impact of the physiology of the cell
- e.g. impacts cancer hallmarkers
- good target
What is the 4 classification for cancer biomarkers
- Predicitive Biomarkers
- can be used for personalised / targetted therapy = improve outcomes - Prognsotic Biomarkers
- estimate OS
- e.g. mutated TP53 (tumour suppressor p53 enxyme) = bad prognosis
- TP53 normal function = detects mutations + causes cell cycle arrest for repair or apoptosis - Diagnostic Biomarkers
- e.g. philadelphia chromosome in CML - Molecular, Physiologic, Histologic, and Radiographic Biomarkers
- identifying speciifc DNA, RNA or protein associated with a specific cancer
What 8 technologies can be used for detection of cancer biomarkers
- Liquid Biopsy
- looking for ctDNA, cfDNA
- DNA Sequencing
- taking sample from tissue or blood + isolating the genomic DNA
- Fluroescent Immunoassay
- complex forms between fluro. dye and DNA
- complex is hybridised by specifc prtotein, if this occurs = presence of cancer protien in tissue
- PCR (polymerase chain reaction)
- identifies mutations
- Molecular hybridisation
- use nucleic acid that will hybridise with a specifc DNA sequence
- Immunohistochemistry
- stain piece of tissue with an antibody
- see if antibody recognises the target
- Electron Microscopy
- identify morphology of tumour cell
- CRISPR / Cas9
- can identify if genes have translocaed
Genomics
-omic suffix = study of | Genomic Process, Use, Technology
Genomics = study of an organisms complete genome / all genes
Genomic Medicine Process:
1. Discovery of genes involved in specific disease
2. Clinical validation
- investigate if gene expression is associated with other things
3. Clinical implementation
- develop drugs that alter gene expression
USE:
- In prognosis, diagnosis and cancer treatment
TECHNOLOGY:
- Next Generation Sequencing (detects multple genomic alterations)
What are functional genomics and comparative genomics
use in diagnosis, disease prevention, prognosis, therapeutic application
Functional Genomics:
- Translation of info. from human genome sequence to personalised medicine
- Interpretting DNA to determine function of genes, RNA and proteins
Comparative Genomics:
- Compare genomes sequence of diff. species
- e.g. human vs mouse / other mammal
- Can identify regions of similarities and differences
What are proteomics
use in diagnosis, disease prevention, prognosis, therapeutic application
Proteomics - large scale study of proteomes
- have many diff. types of proteomics
- e.g. structural and functional proteomics
Proteomes - a set of proteins (prodcued by an organsim)
- NOT constant, changes over time
- differs from cell to cell
- histones (proteins) organise genetic material
- histones = +ively charged, DNA = -ively charged
Sturcutre:
Genome → Transcriptome → Proteome → metabolites
What are metabolomics transcriptions
-omic suffix = study of
Metabolomics - study of metabolites
- investigate metabolic phenotypes
- enables precision medicine
- enable discovery of new targets, niomarkers
Metabolites - small molcecules (e.g. a.acid, dugars, drugs)
What are epigenetics and its importance
Epigenetics - how your behavior / environment can cause changes that affect how your genes work
- epigenetic changes are reversible unlike genetic mutations
- do not change the sequence of DNA bases, BUT change how your body reads a DNA sequence
IMPORTANCE:
- Genomics and Proteomics aren’t enough
- Epigentic changes affect gene expression
Role of epigenome in cancer
On NOTES
- DNA methylation (chemical modification) has a crucial role in many processes
- DNA methylation is catalysed 3 DNMTs
- DNMTs are overexpressed in many cancers
- Methylation of CpG dinucleotides can be a clinically valuable biomarker and prognostic biomarker
