Module 3 - content Flashcards
(26 cards)
1
Q
Cancer as a genetic disease
A
- driven by changes in the genes that control the way cells grow and multiply
- changes include point mutations, chromosomal abnormalities and new foreign genes
2
Q
What genomes do we examine for oncology
A
germline and tumour
3
Q
What is the germline genome
A
- the inherited genome of a person present in every cell
- may contain inherited variants that confer an elevated risk of
- 5-10% of all cancers are hereditary
- can be passed on to offspring
4
Q
What can germline genomes tell us
A
- germline variants
- pharmacogenomics > how a patient might respond to a drug and whether they will have side effects
- helps us to accurately interpret the tumour genome via comparison
- hereditary cancer syndromes
5
Q
What is the tumour genome
A
- present in all tumour cells
- contain entire germline genome +/- any somatic variants
- somatic variants occur throughout life driven by age and modifiable risk factors
6
Q
What can the tumour genome tell us about
A
- actionable (oncogenes, hotspot genes) vs non-actionable genes (tumour suppressor genes)
- microsatellite instability
- mismatch repair deficiency
- tumour mutational burden
- potential resistance mechanisms
- circulating tumour DNA
7
Q
Pathway into oncology for patients
A
- prevention
- screening
- symptoms
- diagnosis
- treatment options
- outcomes
8
Q
Precision oncology diagnosis
A
- utilise a molecular tumour board
- board of multiple experts
- patients have a greater outcome
- can only be done on patients which can afford next generation sequencing > ethics?
9
Q
Cancer treatment options
A
- chemo
- surgery
- radiotherapy
- targeted therapy
- immunotherapy
10
Q
Biomarker guided therapies
A
- BCR-ABL chromosomal rearrangement in CML > target of imatinib
- HER2 > target of trastuzumab in breast cancer
- BRAD V600E > target of vemurafenib and trametinib in melanoma cancers
- PD-1/PD-L1 for immuno
- these are not largely publically funded > ethics?
11
Q
Non-small cell lung cancer biomarker guided therapies
A
- EGFR mutants
- ALK or ROS1 fusions detected via IHC or FISH
- PD-1/PD-L1 detected via IHC
12
Q
Immunosurveillance
A
- dead, stressed or dying cells release antigens and danger signals
- antigens presented by APCs via MHC molecules
- APCs migrate to lymph nodes to prime and activate antigen specific T cells
- antigen specific T cells traffic to the tumour and recognise cancer cells with the matching antigen
- cytotoxic T cells are highjly effective at killing cancer cells
- PD-1/PD-L1 prevents over response
- cancers can mutate proteins creating neoantigens
13
Q
How can cancers escape immunosurveillance
A
- manipulation of immune checkpoints
- Anti PD-1/PD-L1 possible treatments
14
Q
TMB
A
- high TMB are more likely to generate neoantigens = possible biomarker for measuring TMB
- genomics is required to know TMB
- best way to determine is via whole genome sequencing
- need to identify and remove germline variations so they dont inflate the TMB status score
15
Q
Why genomic guided precision oncology would worsen inequities if it was rolled out today
A
- The existing system already underdelivers so new technology is unlikely to address inequities
- Genomics fails on diversity
- biases in research and available data
16
Q
Logistical factors causing bias in research and available data
A
- controlling variables to make it easier
- researchers find it more convenient as its already available data with little variables
17
Q
Historical and systemic factors causing bias
A
- differences in the determinants of health, access to care and quality of care received
- colonisation
- indigenous health is usually affected by racism
- poor experiences with genetic research
18
Q
Poor experiences with genetic research in indigenous groups
A
- researchers lack communication, engagement and cultural competency
- exploitation of genetic material and theft of intellectual property = havasupai tribe
- negative representation of indigenous populations in publications = warrior gene in Maori
19
Q
4 main parts of responsiveness to Maori framework
A
- relevance to Maori
- Maori involvement
- Promoting Maori voice
- governance = how to uphold responsibilities to Maori
20
Q
What does responsiveness to maori ensure we do
A
- do important and relevant research
- prioritise needs
- manage our responsibilities
- avoid previous mistakes
- build excellence and equity into research
21
Q
Relevance of lung cancer research in Maori
A
- higher incidence rates in Maori
- worse health outcomes due to inadequate healthcare and late diagnosis
- lack of representation in existing research
- TMB measurements require germline testing = privately funded = gap
- mistrust with researchers
- pre-existing publications indicate a difference between European and other ethnicities TMB measurements
22
Q
downside of random sampling in Maori vs Non-Maori studies
A
may lead to unequal representation of Maori so there is a decreased statistical power = research question cannot be answered
23
Q
How to ensure safe involvement of Maori in projects
A
- inclusion of researchers who are culturally aware or are directly involved in the community
- an established respected researcher to ensure Maori feel safe and protected
- focus on establishing a relationship
- make sure the community is aware that their data belongs to them
- whanau engagement
- maori data sovereignty
- look at existing research to recruit experts in this field
24
Q
Promoting Maori voice
A
- data analysis needs to reduce overextrapolation and victim-blaming
- think about the context of the study and the inequities in social determinants of health
- extreme care taken when considering genetics
- dynamic consent = ability to change decision in future work
25
Data sovereignty
- managing obligations and expectations
- managing risk
- distributing benefits
- future proofing
- meet treaty obligations
26
Te Tiriti O Waitangi relevant articles
- article 1 = researchers making good and informed decisions
- article 2 = maori self-determination over maori data
- article 3 = equity
