Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000–2020)

Kim, Jeeyun; Ceccarelli, Rachel; Lu, Christine Y.

doi:10.3390/jpm11030179

Cited by 49 publications

(28 citation statements)

References 49 publications

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“…This lack of harmonization is attributed to differences in population allele frequencies, variable genetic test availability and diversity in insurance coverage [236]. The annual proportion of new FDA drug approvals with PGx labeling increased by nearly 3-fold from 10.3% in 2000 to 28.2% in 2020, especially in cancer drugs (75.5%) [237].…”

Section: Future Trendsmentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug–drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.

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Section: Future Trendsmentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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“…An increase in dose from 40 mg/day to 80 mg/day is recommended for NMs only three days after initiation of treatment. Several public resources are available in recognition of the need to translate knowledge of pharmacogenetic variants to clinical practice [69,70]. Table 1 lists examples of medications that have been prescribed for PMS patients [37,[71][72][73][74] as well as published clinical guidelines from CPIC.…”

Section: Pharmacogenomics In Pms With Particular Focus On Cyp2d6 Located At 22q132mentioning

confidence: 99%

Genetic Findings as the Potential Basis of Personalized Pharmacotherapy in Phelan-McDermid Syndrome

Dyar

Meaddough

Sarasua

et al. 2021

Genes

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Phelan-McDermid syndrome (PMS) is a genetic disorder often characterized by autism or autistic-like behavior. Most cases are associated with haploinsufficiency of the SHANK3 gene resulting from deletion of the gene at 22q13.3 or from a pathogenic variant in the gene. Treatment of PMS often targets SHANK3, yet deletion size varies from < 50kb to > 9Mb, potentially encompassing dozens of genes and disrupting regulatory elements altering gene expression, inferring the potential for multiple therapeutic targets. Repurposed drugs have been used in clinical trials investigating therapies for PMS: insulin-like growth factor 1 (IGF-1) for its effect on social and aberrant behaviors, intranasal insulin for improvements in cognitive and social ability, and lithium for reversing regression and stabilizing behavior. The pharmacogenomics of PMS is complicated by the CYP2D6 enzyme which metabolizes antidepressants and antipsychotics often used for treatment. The gene coding for CYP2D6 maps to 22q13.2 and is lost in individuals with deletions larger than 8Mb. Because PMS has diverse neurological and medical symptoms, many concurrent medications may be prescribed, increasing the risk for adverse drug reactions. At present, there is no single best treatment for PMS. Approaches to therapy are necessarily complex and must target variable behavioral and physical symptoms of PMS.

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“…Although, adverse drug reactions are still a challenge [ 3 ]. Pharmacokinetics and pharmacodynamics of the drugs are also influenced by germline gene variants, some already indicated in drug labels [ 4 , 5 ]. The most important genetic risk factors are already described in pediatric ALL as well, however, they failed to reliably predict prognosis [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics of the Central Nervous System—Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia

Sági

Gézsi

Egyed

et al. 2021

Cancers

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Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.

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Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000–2020)

Cited by 49 publications

References 49 publications

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Genetic Findings as the Potential Basis of Personalized Pharmacotherapy in Phelan-McDermid Syndrome

Pharmacogenetics of the Central Nervous System—Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia

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