Genomic medicine takes advantage of the genetic information of an individual to guide medical care decisions, with drug genes tests (also known as pharmacogenomic or PGX) a key application that customizes the needs of genetics based on genetics. Althegh PGX Testing sacrifices a more precise and personalized approach to prescribe medications in a safer and effective way, it benefits both patients and healthy systems, their broad clinical adoption remains limited. The change towards the implementation of PGX tests by medical institutions is promising, but the evidence that supports its broad realization is still arising. A remarkable example of PGX adoption delay is the lack of evidence of genetic variations that can lead to serious toxicities with cancer treatments.
Clinical problem
Chemotherapy has long been an cornerstone in cancer treatment, with medications such as fluorouracil and capecitabine widely used. While thesis medications are effective, overdose can be toxic or even fatal for a small percentage of patients carrying specific variants of the DPyD Gene. The tests of these variants are crucial for the prevention of serious advertisements, since the carriers metabolize fluorouracil and capecitabine incorrectly, which puts them at a high risk of serious toxicity. Revealing these variants with DPyD Tests can help customize cancer treatment and improve patients.
He DPyD The gene produces dihydropirimidine dehydrogenase (DPD), an enzymatic response to metabolize fluorouracil and capecitabine. The DPD breaks down the thesis measurements in the liver to avoid toxic accumulation in the body. However, DPyD Genetic variants can cause partial or complete deficiencies in the DPD enzyme, which leads to dangerously high levels of medicines. DPD deficiency can be detected in 39-61% or patients who experience serious toxicities. Between 3% and 8% of the general population entails a copy of a variant associated with lower levels of the DPD enzyme.
The impact of DPyD variants on treatment results
Patients with DPyD Genetic variants may experience severe toxicity with standard fluorouracil or capecitabine dose. Toxicity may include neopenia that prolongs life, gastrointestinal toxicity, mucositis and manual feet syndrome, which may require hospitalization and could be fatal. In the United States, approximately 275,000 cancer patients receive fluorouracil annually, and it is estimated that 3% develop a certain degree of toxic reaction. Every year, 1,300 patients experience fatal toxicity. Identify patients who carry harmful DPyD Genetic variations through PGX tests before chemotherapy administration are critical to prevent serious thesis toxicities. PGX tests generally cost a few hundred dollars, which is relatively economic compared to the high costs associated with the management of the side effects of chemotherapy.
The Clinical Pharmacogenetics Implementation Consortium, a group of recognized international experts, is a key resource to provide practical and processable clinical recommendations on DPyD Evidence. The group issued a guide to support the safer use of fluorouracil and capecitabine using DPyD Test results. Guidelines recommended by reducing the initial dose in patients with partial DPD deficiency and adjustment dose in subordinate cycles based on tolerigeity. For patients with complete DPD deficiency, alternative medications are incoming. Studies have shown that for patients undergoing pretreatment DPyD Tests, the incidence of serious hospitalizations related to toxicity decreases significantly, and the number of deaths decreases.
Why DPYD tests are crucial for cancer care
Test of DPyD Varants is essential to improve cancer care and ensure that patients receive chemotherapy in the safest and most effective way. In Europe, guidelines have recommended preventive DPyD Tests since 2020 and pretreatment tests are becoming a standard practice. In the United States, the Food and Medicines Administration (FDA) has taken multiple measures in recent years to address the risk of severe fluorouracil toxicity and capecitabin. In January, the FDA issued a security advertisement that emphasizes the importance of oncological care teams knowing the DPD deficiency risks and informing their patients about these risks. The agency also informed the Oncology community that the tests are available and encourages oncologists to consider trying patients for DPD deficiency before the treatment begins. Until recently, only 3% of American oncologists ordered DPyD Evidence.
With the new FDA security announcement, the pharmacogenomic community expect hospitals to create effective preventive protocols DPyD Oncology environments, which will increase the adoption of pretreatment tests. This month, the National Integral Cancer Network updated its treatment guidelines for colon cancers, anal, rectal and small intestine to recommend that oncologist discussion DPyD Tests with patients before prescribing chemotherapy. Guidelines emphasize the importance of considering the patient’s individual circumstances when making treatment decisions. While guidelines do not completely admit universal evidence, patient defenders see this as a movement in the right direction.
DPYD test modalities optimization
There are several challenges to do DPyD Test routine in clinical practice. A significant obstacle is the complexity of genetic tests in itself. Different laboratories offer several panels or variables, and not all panels are integral or represent the full range of variants observed in ethnic populations. For example, common variants may be well documented in individuals or European descent, but less recognized in other populations, such as those of Asian or African ancestry. This can lead to lost diagnoses or improper treatment settings in non -European populations.
At least four DPyD The variants in Europeans are widely recognized in the prescription labels of fluorouracil and capecitabine FDA for association with severe toxicity. Recent work has identified other harmful variants in patients with African and Asian genetic ancestors, offering the opportunity to establish standards to design tests that will benefit a multiethnic population. The Association for Molecular Pathology issued a set of guidelines in the supervision of 2024 that must be tested that the least patios are lost, especially those of non -European populations.
Widening the wider PGX tests in cancer attention
An analysis of the real world or 22,223 cancer patients found that 88.3% of them received at least one medication affected by the PGX variants, for which there are processable recommendations. These medications are used to handle cancer or other conditions that can coexist or be triggered by the disease or its treatments. Cancer patients frequently receive support PGX measurements to handle pain, nausea, depression, anxiety, neurological symptoms and cardiovascular disorders of cancer treatment duration. The value of the PGX tests of gene genes, which covers DPyD And other important genes, allows oncology team not only cancer medications but also all other medications affected by genetics. The use of a personalized care plan increased with PGX Insights, ideally at the time of diagnosis, increases the confidence of the care team and facilitates the patient’s partipation in the creation of a custom care plan. Establishing a unique PGX firm for each patient allows the reuse of the results of the tests for future treatment decisions. Moreover, economic modeling has shown that the use of a multiple gene panel test at the beginning of the treatment is associated with greater profitability.
Tips for the effective implementation of DPyD evidence
Implementers are encouraged to establish protocols and policies throughout the hospital for preventives DPyD Tests before the relevant treatments begin. The implementation of the tests must be integrated into the existing clinical workflows to ensure easy access to the request for tests and the acquisition of results. It is essential to involve orders providers at the beginning of the process and train them on the importance, interpretation and dose adjustments based on the test results. To climb and maintain a DPyD Test program, organizations must collaborate with experienced software partners that surround longitudinal digital health platforms that expand beyond the integration of laboratory tests. The solutions that allow doctors to perform all operations for their genomic workflows within electronic health systems and provide tools for supporting decisions are positioned to ensure that a program is scalable and sustainable.
Althegh, the health industry has a long way for PGX tests for DPyD and other genes extend, it is an encouraging that regulatory agencies and professional organizations are making recommendations and collection between medical care. The introduction of such tests will help oncologists and other doctors improve the results of patients, reduce costs and minimize risks.
Editor’s Note: The author is a member of the Scientific Consortium of the Clinical Pharmacogenetics Implementation Consortium (CPIC)
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Photo: Liana Nagieva, Getty Images
Houda Hachad, Vice President of Clinical Operations, Aranscia, is a member of the Scientific Advisory Council of the Clinical Pharmacogenetics Implementation (CPPP) and is an active member of the Pharmacogenic Variation Consortium (Pharmvar). It is involved with several working groups and pharmacogenomic committees aimed at standardizing the modalities of pharmacogenomic tests and facilitating its adoption by the clinical community. Houda is excessively the development of extensions of the pharmacogenetic products line from the beginning to the delivery and headed the operational efforts to translate technology solutions of exact scientific.
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