6.5 Wk-5 Precision vs Personalised medicine. Flashcards
What is pharmacogenetics?
An analysis to predict drug
* Efficacy
* Safety
How has the price of genomic sequenciing evolved
- 2001 - 100,000,000
- 2021 - 1000
Why bother?
- Initial treatment in a variety of disease, does not work
- Important in oncology because all cancers are different.
What is the difference between precision medicine and personalised medicine?
Precision medicine relates to the drug or technology itself.
Personalised medicine relates to the art of ensuring the right patient, gets the right drug at the right dose at the right time
How has the approach to medicine evolved over time?
Traditional medicine - every patient gets the same treatment for the same condition
* e.g. Pain relief – Aspirin
Stratified medicine – Patients are stratified into groups and each group gets the same medicine.
* e.g. Trastuzumab – HER2 breast cancer.
Personalised medicine – Tailored medicine for a single patient
* Chimeric antigen receptor “T” cell therapy
* CAR T cell therapy.
What are the 2 causes of gene mutations?
Inherited mutations – CFTR gene mutations leads to cystic fibrosis.
External factor induced mutations – Smoking/Chemicals/Radiation
What type of mutations are linked to oncogenesis?
Mutations in genes which are linked to cell death and cell proliferation
In an ideal world how might these mutations be detected?
Rather than conduct a full gene sequence on each patient
If you know the mutations you are looking for – Targeted Gene Panel analysis
If you are not sure which mutations are causing the disease – Exome gene panel analysis
If you don’t know what is happening – Full genomic sequence.
What mutations might contribute to the hallmarks in cancer?
Cancer is self sufficient in growth signals
* Activate H RAS oncogene
Cancer is insensitive to anti growth factors
* Lose Retinoblastoma supressor gene
Evade apoptosis
* Produce IGF survival factors
Limitless replicative potential
* Turn on Tolemerase
Sustained angiogenesis
* Produce vascular endothelial growth factor inducer
Invade local tissue cause metastases
* Inactivate E-Cadherin
How many mutations does it take to cause cancer?
Typically more than 1
Is inflammation an emerging hallmark of cancer?
Yes
Tumour cells can cause inflammation
Cytokines are released from the inflamed cells, leading to angiogenesis of the tumour
Inflammation may also lead to the release of free radicals which damages DNA
What is the BRCA1 & BRCA2 mutation?
The BRCA1 gene is a human suppressor gene
* It reduces cell division and helps to repair DNA breaks
In Breast cancer BRCA1 Is often mutated
* Allowing cell division +++
Only 12% of patients with breast cancer have a normal BRCA1 gene
* 55%+ have BRCA1 mutation
* 45%+ have BRCA2 mutation
What is PARP
Poly (ADP-ribose) polymerase 1 (PARP1) is an ADP-ribosylating enzyme essential for initiating various forms of DNA repair.
What is the role of a PARP inhibitor?
Inhibit PARP with PARP inhibitor e.g. Olaparib
* If BRCA1 & BRCA2 wild type (Not present)
* No effect
Inhibit PARP with PARP inhibitor e.g. Olaparib
* WHEN BRCA1 and BRCA2 mutation present
* Attacks tumour cell
NB You have to check that the breast cancer patient has the BRCA1 and BRCA2 mutation, if not it does not work.
What is the role of the Epidermal growth factor receptor in breast cancer?
Typically mutated in breast cancer patients
The goal is to block the receptor using monoclonal antibodies
If the Tumour is KRAS wild type (KRAS not present)
Cetuximab, is a MAB which binds to and inhibits the activity of EGFR, leading to reduced cell proliferation
If the Tumour is KRAS positive mutation
Cetuximab, does not work.
Therefore a genetic test for KRAS mutations has to be performed prior to treating a patient with cetuximab
