ABCC2 (ATP Binding Cassette Subfamily C Member 2)

Analysis of the expression of HML-2 and its association with CpG methylation contributes to a comprehensive interpretation of the CRC pathogenesis mechanisms.

The results showed that deoxypodophyllotoxin synthase (2-ODD), secoisolariciresinol dehydrogenase (SDH) and coumarate 3-hydroxylase (C3H) were essential genes that lead to the PTOX content differences in S. hexandrum from different provenances, WRKY and AP2/ERF-ERF were considered to be key transcription factors, and ABCE1 and ABCC2 were the primary transporters. The results can provide a new perspective and excellent genes for revealing the cause of the different PTOX contents in S. hexandrum from different provenances.

Overall, our findings showed that an adjustment of the initial asciminib dose may be needed based on genotyping information for the NR1I2 -25385C > T polymorphism and the body weight of the patient; however, further prospective studies are necessary.

The review also highlights the pharmacokinetic implications of, e.g., tacrolimus, digoxin, and metformin. Potential therapeutic interventions are also covered (diet, pre-/probiotics, fecal microbiota transplantation, modulation of PXR/FXR/AhR pathways). Considering the microbiota as a "second genome" enables more accurate prediction of drug exposure, reduction in toxicity, and optimization of dosing for orally administered preparations.

UGT1A1*6 and ABCC2 -24C > T variants emerge as potential predictors of irinotecan-induced neutropenia, while UGT1A1*6 and SLCO1B1 521T > C may serve as markers of prolonged PFS in Thai patients. Validation through larger prospective studies is essential to confirm and refine these genetic associations.

Therapeutic combination index analysis indicated robust synergy between FMNT and 5-FU, with combination therapy achieving superior tumor growth inhibition compared to monotherapies. Collectively, our findings uncover a novel miR-490-3p/ABCC2 regulatory mechanism underlying FMNT's antitumor activity and highlight its potential for chemosensitization through ABCC2 inhibition, providing a strong rationale for flavonoid-based adjuvant therapy in CRC management.

Although particular attention was paid to elucidating the underlying mechanisms, current knowledge in this area remains limited. Moreover, extensive in vivo and clinical studies validating these findings are still lacking, emphasizing the need for further research to evaluate their translational potential.

© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Protein stability analysis confirmed their destabilizing effects, while functional enrichment highlighted their involvement in key pathways driving tumorigenesis. This study identified 11 key DEGs harboring potentially pathogenic novel missense variants, highlighting vulnerabilities for precision-targeted therapies in EC.

However, this review emphasises caution in targeting ABCC5 for cancer therapy due to its underappreciated physiological function(s), particularly in the brain and male reproductive system. Understanding ABCC5's substrate specificity, regulatory mechanisms, and functional redundancy with its paralog ABCC12 remains critical for successful therapeutic strategies in humans.

The C allele of the ABCC2 gene, with a methotrexate cutoff greater than 4.5081 ng/ml, and the MTHFR T polymorphism are strongly associated with toxicity. The risk of toxicity in individuals receiving methotrexate can be predicted with a threshold value of 4.5081 ng/ml for methotrexate levels; however, there was no significant variation in homocysteine levels across the groups.

Further, western blot results exhibited that TAM combined with RUT reduced the expression levels of Nrf2, GCL, GLS, and SLCA711 proteins in LCC2 cells, which was corroborated by molecular docking. TAM and RUT combination may provide a promising treatment pathway to conquer TAM resistance and hence extend the life expectancy in breast cancer patients.