An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean

Abstract

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology

“…These challenges encompass the formulation of extensive PGx clinical guidelines to guide treatment decisions across a culturally and genetically varied patient base. Moreover, there is a pressing need for rigorous cost-effectiveness analysis, suitable regulatory frameworks, and increased gene/drug trials ( Quinones et al, 2014 ; López-Cortés et al, 2017 ; Salas-Hernández et al, 2023 ).…”

“…Despite significant advances in precision oncology through international consortium efforts like The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ( Spratt et al, 2016 ; Guerrero et al, 2018 ), the underrepresentation of diverse ethnic backgrounds in many cancer research studies has led to a significant bias toward Caucasians in cancer genomic databases ( Guerrero et al, 2018 ). This bias poses a considerable obstacle to the advancement of PGx and precision oncology, especially in developing regions ( Salas-Hernández et al, 2023 ). To bridge this gap, the primary objective of our study was to conduct an integrated in silico analysis to identify actionable genomic alterations in gastric cancer, evaluate their impact through deleteriousness scores and allele frequencies across nine global populations, and prioritize targeted therapeutic strategies.…”

The pharmacoepigenetic paradigm in cancer treatment

“…In summary, the exploration of pharmacogenomic and epigenetic biomarkers in post-treatment evaluation opens new avenues for personalized medicine in cancer treatment, offering insights into patient prognosis, the efficacy of therapy, and potential future strategies in disease management based on the ethnicity ( Paz-y-Miño et al, 2010 ; Paz-Y-Miño et al, 2015 ; López-Cortés et al, 2017b ; 2020 ; López-Cortés et al, 2018 ; Yumiceba et al, 2020 ; Salas-Hernández et al, 2023 ).…”

Why is There Still Debate About Recommending DPYD‐Testing Before Fluoropyrimidine Treatment?

“…The question comes up, why is DPYD testing not yet recommended globally, 15 see also some examples of capecitabine drug label annotations from different regulatory agencies (Table 1). As outlined in the article of Hertz et al ., 1 the clinical practice guidelines from the US National Comprehensive Cancer Network (NCCN) is still not endorsing pretreatment testing of DPYD and this was used as a rational for the FDA to not recommend testing.…”