Tuesday, June 21, 2022

Clinical Genomics Career Panel webinar series 2022

ClinGen is hosting a Clinical Genomics Career Panel webinar series this summer for individuals interested in career in clinical genomics. Sessions are moderated and panel members will discuss their work and career paths. All are welcome to join!

PharmGKB Acyclovir/Ganciclovir Pathway Published

The PharmGKB Acyclovir/Ganciclovir Pathway has recently been published in the journal Pharmacogenetics and Genomics.

Acyclovir (ACV) and ganciclovir (GCV) are commonly prescribed antivirals to treat infections caused by herpes viruses, varicella-zoster virus or cytomegalovirus (eg. cold sores, shingles and chicken pox, etc.). The pathway, co-developed by Maud Maillard along with other members of the Yang Lab in St. Jude, as well as members of the PharmGKB team, outlines the metabolism, transport, and mechanism of action of ACV and GCV with a view to decipher the existing interpatient variability, and highlights pharmacogenomics implications by the variants of the NUDT15 and ABCC4 genes on ACV and GCV efficacy.  Further work is needed to validate these findings and discover other candidates, with the aim of optimizing antiviral therapy.


View the interactive pathway on PharmGKB:
Acyclovir/Ganciclovir Pathway, Pharmacokinetics/Pharmacodynamics


Read our new publication:

PharmGKB summary: acyclovir/ganciclovir pathway
Maud Maillard, Li Gong, Rina Nishii, Jun J Yang, Michelle Whirl-Carrillo, Teri E Klein
Pharmacogenet Genomics. 2022 Jul 1;32(5):201-208. Epub 2022 May 30.

PMID: 35665708

View all pathways on PharmGKB.

Thursday, June 2, 2022

Expansion of pharmacogenetics education agreed as part of lawsuit settlement

Oregon Health & Science University (OHSU) will introduce new educational initiatives on the risks of prescribing the chemotherapy drug capecitabine to patients with DPD deficiency as part of a lawsuit settlement.

The settlement was reached with Joanne McIntyre, whose husband David died as a result of severe capecitabine toxicity. David carried variations in the gene DPYD, which encodes the DPD enzyme. DPD is involved in metabolism of fluoropyrimidine drugs, including capecitabine. Variants in DPYD, such as those that David carried, can inactivate the DPD enzyme, leading to DPD deficiency. Patients with DPD deficiency are unable to properly metabolize capecitabine and other fluoropyrimidines, and are at risk of experiencing severe drug toxicity. In David's case, this toxicity was fatal.

PharmGKB has annotations of several clinical guidelines for capecitabine and DPYD, including those from CPIC and the DPWG. These guidelines uniformly recommend either a dose reduction or selection of an alternative drug in patients with DPD deficiency.

OHSU will hold seminars to educate clinicians on the risks associated with DPD deficiency, how to identify severe capecitabine toxicity in patients and how to administer the antidote. They will also include a module on the topic in their fellowship program and provide a written resource guide to staff in their oncology department. Going forward, patients identified as candidates for capecitabine chemotherapy will be informed of the risks associated with DPD deficiency and, where appropriate, will be offered testing.

We at PharmGKB applaud Joanne's singular dedication to saving patients' lives and OHSU's commitment to implement these changes. Resources on capecitabine pharmacogenomics, including annotations on clinical guidelines for the use of DPYD genotypes in capecitabine prescribing, can be found at the PharmGKB capecitabine drug page.