Jeanne Petit, Pharmacy Resident at IUCT-Oncopole, shared on LinkedIn:
“CYP2D6 is involved in the metabolism of approximately 20% of commonly used medications. This includes tamoxifen, a key treatment in the management of hormone receptor-positive breast cancer.
Yet, part of the interindividual variability in treatment response remains unexplained.
I am delighted to share our latest study, which aimed to evaluate the added value of whole-gene CYP2D6 next-generation sequencing (NGS) in patients treated with tamoxifen.
This work, published in Clinical Pharmacology and Therapeutics, was the focus of my Doctor of Pharmacy thesis, supervised by Dr. Fabienne Thomas. I would like to warmly thank Pr. Nicolas Picard for presiding over my thesis jury, as well as Pr. Saint-Marcoux Franck, Pr. Etienne Chatelut, and Dr. Abd-El-Kader Ait Tayeb for sharing their expertise and for the quality of their discussions.
Title: Does Next Generation Sequencing (NGS)-Based CYP2D6 Sequencing Improve Genotype-Phenotype Concordance in Tamoxifen-Treated Patients?
Authors: Jeanne Petit, Julien Plenecassagnes, Aurelie Brice, Florence Dalenc, Ludovic Mallet, Etienne Chatelut, Ayman Al Saati, Fabienne Thomas
Read the full article.
Interindividual variability in drug response remains a major challenge in clinical pharmacology. Pharmacogenetics provides valuable insights to address this challenge by enabling treatment decisions to be tailored according to the patient’s genetic profile.
In this context, we investigated a cohort of patients treated with tamoxifen to explore the limitations of conventional CYP2D6 genotyping approaches.
Our results confirm that the alleles commonly assessed by targeted genotyping methods capture the vast majority of actionable variants in our population. The added value of NGS mainly lies in refining the predicted metabolic phenotype through improved detection of structural variants, which may be misclassified as functional copies by conventional approaches.
This work also highlights the ongoing challenges associated with rare and variants of uncertain significance, which are more frequently observed in populations that remain underrepresented in genomic studies. The clinical data collected in this work therefore contribute to improving their characterization.
These findings highlight the limitations of targeted genotyping and support a reasoned integration of NGS into pharmacogenetics, taking into account both clinical considerations and economic constraints. This approach appears particularly relevant for highly polymorphic genes such as CYP2D6, especially in situations of genotype–phenotype discordance.”
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