Week 8 - The relevance of "omics" in clinical oncology Flashcards
(13 cards)
What is Precision Oncology
Making tailored Rx based on pts omics data.
- Use bioinformatics tools + evidence-based guidance to prescribe drug that best matches characteristic of each pt
What is the need for development of molecular targeted therapies
More personalised = better pt response
Look at Pt:
- Genome (isolate DNA)
- Tumour histology in comparison to normal tissue
- see differences in products expressed
- NGS (
What is the difference between targeted therapy and standard chemotherapy
Targeted Therapy:
- Acts on specific molecular targets found on tumour cell
- Cytostatic = stop cell proliferation / inhibit pathway
- can kill, but is targetted
Chemotherapy:
- Acts on ALL rapidly dividing cells inc. normal cells
- Cytotoxic = kills all cells = many SE
List methods of tumour stratification for the selection of optimal therapeutic modalities
How can gene expression profiles be used as surrogates for biological phenotypes
- Isolate cells + grow in a petri dish
- see what profile is obtained - Can inject isolated cells into mice
- See if mice obtain same profile
- e.g. if state B mice were give state A cells do they develop state A phenotype - If profile is same = gene plays no role in disease developement
How can genome sequencing faciliate development of medicine
i.e. the process
- Isolate DNA from blood drawn from pt
- Create a library from the DNA and perform sequencing
- can sequence whole genome or exome
- exome ~ genes overlyexpressed in cancer compared to normal
- Align the sequences of the normal pt and cancer pt
- Identify target in cancer pt (e.g. overexpressed gene)
- Identify pathogenetic variants (e.g. mutation)
- Decide drug OR develop new drug based off findings
Next Generation Sequencing (NGS) relevance to clinical practice
Allows identification of:
- Mutations (nucleotide variants)
- Transloactions of proteins (new fusion proteins)
- DNA methylation (genome modification)
- methylation can cause suppression of receptors
Beneficial in clinical interpretation
- If know expression of specific gene relates to cancer development can state pts cancer risk, OS (i.e. high or low)
- If gene contributes to phenotype of disease
Transcriptomics relevance to clinical practice
Signatures can be obtained from tumour tissue
- Can analyse tumour tissue from 2 stages e.g. before and after treatment
- to anlayse response
- see if drug benefitted pt
- Can compare tumour tissue to normal tissue
- too see diff. in gene expression
Epigenomics relevance to clinical practice
What are epigenetics, HEP
Epigenetic changes are tissue specific + can be inherited
Epigenetics:
- Changes to how your body reads a DNA sequence
- behaviors / environment can cause changes that affect the way your genes work
- Unlike genetic changes (mutations), epigenetic changes are reversible and do not change the sequence of DNA bases
HEP (Human Epigeneome Project)
- Identify + interprets genome-wide DNA methylation of all human genes
What are the 2 common epigenetic changes
- DNA Methylation
- Occurs on histones attached to DNA
- MoA: methyl group added to cytosine
- Methylation of histones = DNA becomes more tightly packed in cells
= inaccessible by transcription factors = low expression of tumour suppressors
- Pts with ↑ methylation = ↓ suppressors
- TARGET: drugs that prevent methylation - DNA Acetylation
- Occurs on histones attached to DNA
- Acetylation of histones = DNA becomes more relaxed
= accessible to transcription factors = oncogene is expressed
- Oncogenes produce oncoproteins = proliferation, anti-apoptoic genes stimulated
How is histone modification targetted
Epigenetic changes
Drugs which target histone modification in chromatin
- Inhibitors of Methylation and Acetylation can NOT be used ALONE
- used with other anti-cancer drugs
Inhibition Effects:
- Enhance effects of immune checkpoint inhibitors
- Effects on signal expression
- Effects on cytoplasmic signalling
What are the 2 main challenges associated with the precision in cancer treatment
- Who to treat
- improve identification of pts needing treatment
- pt profile, outcomes
- How to treat
- identify effective therapeutic opportunities
- Look at histopathology, genome, tumour profile, NGS
What is the role of pharmacists in optimizing the use of anticancer drugs
- Patient education
- supprt, explain how treatment works, process, correct false info
- Dose adjustments
- depenging on age, organ function, weight - Fomrulation changes
- IV to oral etc. - Pallative Care
- Prevention / Monitoring of ADRs
- Immunisation advice
- Infection prevention support
- Discontinuation of drugs
