Pharmacogenomics in Clinical Practice Session Objectives

Applications of Genomics in Practice

• Genomics is the study of the genome, and all the associated technologies, involving the interpretation of the genome and clinical action.
• Genomics has various applications in practice, including rare disease diagnosis, cancer diagnosis, and pharmacogenomics.

Rare Disease Diagnosis

• Whole Genome Sequencing (WGS) can be used to compare patients with the same condition to reveal patterns and identify genetic causes.
• WGS can help in the diagnosis of rare diseases, reducing the diagnostic odyssey and enabling targeted treatments.

Cancer Diagnosis

• Genomics can be used to identify mutations associated with cancer, both somatic and germline.
• This information can be used to develop preventative and targeted treatments for cancer.

Cystic Fibrosis

• Cystic Fibrosis (CF) is an inherited disorder that affects the cells that produce mucus, sweat, and digestive juices.
• CF causes severe damage to the lungs, digestive system, and other organs in the body.
• The CFTR gene was discovered in 1989, which raised hope for the treatment of CF.
• Over 100 labs have come together to identify over 2000 mutations in the CFTR gene, leading to a better understanding of genotype-phenotype correlations.
• Mutation-specific therapies have been developed to target CFTR mutations.

Physiopathology of Cystic Fibrosis

• CFTR is a phosphorylation-regulated Cl- channel that is comprised of 1480 amino acids organized into 5 functional domains.
• The correct functionality of these 5 domains is needed to control the channel activity.
• The CFTR gene is responsible for regulating the transport of salt and water in the body.

Pharmacogenomics

• Pharmacogenomics is the study of how a patient's genome can influence how they respond to medicines.
• Pharmacogenomics can help in the development of personalized medicine, where treatment is tailored to an individual's genetic profile.
• Pharmacogenomics is used in the treatment of CF, where CFTR modulators are used to target specific mutations in the CFTR gene.
• Pharmacogenomics is also used in cancer treatment, where genetic testing can help identify patients who are likely to respond to specific treatments.

Pharmacogenomics in Cystic Fibrosis

• Kalydeco (ivacaftor) is a potentiator of the CFTR protein that is used to treat gating mutations.
• Orkambi (lumicaftor/ivacaftor) and Symkevi (tezacaftor/ivacaftor) are CFTR modulators that are used to treat specific mutations in the CFTR gene.
• Triple therapy, Kaftrio (elexacaftor/tezacaftor/ivacaftor), is used to treat patients with the F508del mutation.
• Strict commissioning criteria must be followed for eligibility in certain mutations.

Oncology and Pharmacogenetics

• Pharmacogenetics is the study of how variation in a single gene can impact on variability in the body's response to one specific medicine.
• Pharmacogenetics is used in cancer treatment to identify patients who are likely to respond to specific treatments.
• Genetic testing is used to identify patients with genetic mutations that can affect the efficacy of certain treatments.
• Examples of genetic tests used in cancer treatment include TPMT, NUDT15, UGT1A1, CYP2D6, and G6PD.