Personalised genomics: bench to bedside Flashcards
Uses of personalised genomics
Grouping patients based on risk of disease or response to therapy
- Therapy selection
- Group subpopulations uniquely susceptible to a disease or responsive to a specific therapy
Tailoring treatment to the individual characteristics of each patient
What does personalised medicine use?
Combines knowledge about a person (genes, proteins and environment) to predict disease susceptibility, prognosis or treatment response
What does stratification mean?
Division of patients with a particular disease into subgroups based on a specific characteristic who respond more frequently to a particular drug or are at a decreased risk of side effects in response to a certain treatment
What is personalised medicine?
Tailoring therapy to the individual patient
What is precision medicine?
Targeting patients to specific therapies
What is statified medicine?
Separating patients to therapy groups
What percentage of patients respond positively to a drug?
30-70%
Why is stratified medicine useful?
The one-size-fits-all drug approach is dysfunctional, since patients vary in their response to the same drug due to genetic variations found between different individuals
What does stratified medicine provide?
More inclusive patient groups allowing for everyone to have a positive respond to the drug tested
What are the two aims of patient stratification?
Improve outcomes
Reduce adverse events
Examples of targeted therapies
Hormone therapies
Signal transduction inhibitors
Gene expression modulators
Apoptosis inducers
Angiogenesis inhibitors
Immunotherapies
Monoclonal antibodies
Goal for hormone therapy
Slow or stop the growth of hormone-sensitive tumours
For which cancers have hormone therapies been approved?
Breast cancer
Prostate cancer
Goal of signal transduction inhibitors
Block the activities of molecules that participate in signal transduction
What is a key feature of regarding signal transduction pathways?
The mutations are mutually exclusive
So a cancer cell is dependent on the mutation of just one of the signalling pathways
Two signalling pathways cannot be mutated at the same time
How do gene expression modulators work?
Modify the gunction of histones or other epigenetic proteins that play a role in controlling gene expression
Goal of monoclonal antibodies
Deliver toxic molecules
What information is obtained from Sophia genetics?
Reports mutation in cancer to
- define pathogenicity
- identify cancer drivers
- highlight publications and potential existing therapeutic options
What is the most difficult jobs for bioinformaticians?
Analyse the data and decipher what is important and what is not
Needs to clear out all the non-deleterious SNPs and genomic data to identify driver and germline mutations
Why is there no point in looking at all of the genome for identifying cancer mutations?
40-50% of cancers are caused by the same mutations to JAK/STAT or KRAS
The rest of the mutations have no therapy
Which mutations cause most of the cancers?
JAK/STAT
KRAS
Are drugs the only way personalised medicine can be used for?
NO
Can also be applied for other types of therapy
Examples of genomic markers being used for extra-pharmacological therapies
Current treatment for bladder cancer is chemotherapy and radiotherapy
Two predictive markers have been identified which can help treatment selection of either surgery or radiotherapy
AIMP3 and ERCC1
What is AIMP3?
Positive predictive marker for radiotherapy
Translocated to the nucleus in response to DNA damage, helping apoptosis
