Pharmacogenomics in CF and Oncology PDF

Pharmacogenomics: The Use of Genomic medicine □ Genomics- study of the genome and all associated techniques □ Genome-complete set of DNA Applications of genomics in practice: Rare disease: ▪ Comparison of WGS of patients with the same condition to reveal patterns ▪ Diagnostic odyssey ▪...

Pharmacogenomics: The Use of Genomic medicine □ Genomics- study of the genome and all associated techniques □ Genome-complete set of DNA Applications of genomics in practice: Rare disease: ▪ Comparison of WGS of patients with the same condition to reveal patterns ▪ Diagnostic odyssey ▪ Targeted treatments- precise and personalised medicine Cancer: ▪ Identifying mutations associated with cancer-somatic and germline ▪ Preventative and targeted treatments Cystic fibrosis: ▪ Gen discovered in 1980s,therapy targeting genes dysfunctionalities Pharmacogenomics: ▪ Study of how genes affect a person's response to medicines Pharmacogenetics Vs pharmacogenomics: → Pharmacogenetics-study of how variation in a single gene can impact on variability in t specific medicine (large single variant effect) → Pharmacogenomics-study of how a patient's genome can influence how they respond t in many genes)  in CF and Oncology the body's response to one to medicines (many variants Pharmacogenomics: CF ▪ CF- inherited disorder affecting cells that produce mucus, sweat and digestive juices. ▪ CF causes severe damage to lungs, digestive system and other organs in the body. Epidemiology: □ 7000 patients suffer from CF in the world □ 1 in 25 people are carries □ Mainly affects Caucasian population □ Median age of survival increasing Impact of discovery of CTFR gene: □ 1989-Milestone in the history of CF gene □ Over 100 labs came together-over 200- mutations to date identified □ Better understanding of genotype/phenotype correlations  □ Median age of survival increasing Impact of discovery of CTFR gene: □ 1989-Milestone in the history of CF gene □ Over 100 labs came together-over 200- mutations to date identified □ Better understanding of genotype/phenotype correlations □ Improved diagnosis and management of CF □ Mutation-specific therapies. Pathophysiology of CF: w CTFR- phosphorylation regulated chloride channel w Comprised of 1480 amino acids organised into 5 functional domains CTFR modulator therapies:  CTFR modulator therapies: Kalydeco (ivacaftor): Potentiator of CTFR protein (opening channel) Monotherapy w Gating mutations class 3- e.g. G551D w Conductance- R117H w Licensed from 4 months old Interactions:  Interactions: ◊ Avoid CYP3A inducers- rifampicin (sub-therapeutic) ◊ CYP3A inhibitors- reduce dose e.g. grapefruit/Seville oranges ◊ Monitor: LFTs and cataracts ( condition which causes lens of eye to become cloudy leads to vision loss) Pharmacogenomics oncology: Targeted treatment:  DPYD pharmacogenetic testing: ○ DPD- dihydropyridine dehydrogenase- an enzyme ○ Enzyme is coded for by the DPYD gene ○ Involved in the metabolism pathway of 5 fluorouracil, capecitabine and tegafur. Prescribed mainly in GI, breast and neck cancers ○ DPD deficiency-caused by inherited variants of the DPYD gene (germline mutation) ○ Treatment of patients with DPD deficiency- increases risk of serious and fatal toxicities e.g. stomatitis, mucosal inflammation, neutropenia, neurotoxicity DPYD variants tested on NHS