SLC28A3 (Solute Carrier Family 28 Member 3)

Furthermore, we identified alternatively spliced variants of the AS1 lncRNA that differentially regulate CNT3 gene expression, doxorubicin transport, and cytotoxicity. Together, these findings suggest that antisense and splicing mechanisms may be exploited to modulate CNT3 function to reduce doxorubicin cytotoxicity, enabling the development of predictive biomarkers and chemotherapeutic management of anthracycline toxicities.

Analysis of ClinPGx/PharmGKB data emphasizes ABCB1 as a potential resistance marker and supports pre-treatment genotyping of genes like TPMT and NUDT15 to prevent severe toxicities. Future advances should include the expansion of pharmacogenetic studies in underrepresented populations and the clinical validation of new markers in prospective trials, aiming to consolidate precision medicine as a routine part of the therapeutic management of acute leukemias.

As a result, 20 studies were included (15 case-control and five cohorts), revealing several genes and variants associated with cardiomyopathy, among which, SLC28A3-rs7853758, RARG-rs2229774, P2RX7-rs208294 and P2RX7-rs3751143 variants gave the most consistent findings. This review highlights the necessity to establish a set of clinically useful genes and variants to identify patients most at risk of developing cardiomyopathy, and to implement monitoring and prevention strategies.

For methotrexate, the genes ABCC2, MTHFR, and SXR were associated with myelosuppression and hepatotoxicity...This review highlights the complexity and variability of pharmacogenomic associations with chemotherapy-induced toxicities in pediatric oncology. While certain genetic variants show associations with specific toxicities, larger multinational/center studies are needed to strengthen the associations and improve clinical guidelines.

The most studied genes were TPMT and CYP3A5, which are involved in the metabolism of 6-mercaptopurine (6-MP) and vincristine, respectively...Chemotherapies frequently studied were 6-MP (reported in five studies), vincristine, cyclophosphamide, and methotrexate...However, research remains regionally limited, and gaps in infrastructure and healthcare worker training persist. Expanding research efforts and improving pharmacogenomics capacity through pharmacist training and capacity-building initiatives are essential to advancing personalized medicine in Africa, ultimately improving treatment outcomes for pediatric cancer patients.

IRRS accurately predicts disease prognosis and immune status in patients with endometrial cancer. SLC38A3 serves as a prognostic marker for these patients and can be stably targeted by periodate-oxidized adenosine.

Among the polymorphisms examined, 14 across 13 genes showed significant associations with MTX-PG2-5 levels, even after adjusting for the false discovery rate (ABCC5, ATG16L1, CEP72, FSTL5, GMPS, HTR3A, IMPDH1, NT5C2, SLC28A3, SLCO1B3, SUCLA2, TPMT, and TYMS). This study enhances our understanding of genetic polymorphisms in MTX metabolism and therapeutic monitoring for MTX maintenance, promoting personalized medicine in acute lymphoblastic leukemia patients.

This is the first study in the Turkish population to investigate the correlation between the cardiotoxicity risk and 3 marker genes, which are recommended in the pharmacogenetic guideline for risk assessment in pediatric doxorubicin patients. The gene polymorphism that we investigated in this study was useful for the early prediction of cardiotoxicity risk.

Our results imply that instead of a single-SNP approach, SNP-SNP combinations in multiple genes in drug pathways increases the robustness of prediction of toxicity. These results further provide promising SNP models that can help establish clinically relevant biomarkers allowing for greater individualization of cancer therapy to maximize efficacy and minimize toxicity for each patient.

P2, N=450, Recruiting, Mayo Clinic | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=450, Recruiting, Mayo Clinic | Trial primary completion date: Jul 2024 --> Dec 2023