Oestrogen receptor (ER)-positive breast cancer is one of the common forms of breast cancer affecting women worldwide. ER-positive breast cancer patients are subjected to antioestrogen therapy such as selective oestrogen receptor modulator (SERM) and aromatase inhibitors (AIs). Recently, the emergence of resistance to anti-oestrogen treatment is under intensive focus. The different mechanisms postulated to explain the occurrence of resistance in ER-positive breast cancer treatment include the loss of ER function and the crosstalk between signalling pathways in cancer cells. Recent literature highlighted that the cholesterol biosynthesis pathway acts as a novel mechanism underlying resistance to oestrogen deprivation. The present study aimed to highlight the role of cholesterol biosynthesis in anti-oestrogen treatment resistance, putatively suggesting an alternative plant-based treatment using andrographolide from Andrographis paniculata. The hypolipidaemic effect of andrographolide can be utilised to prevent the resistance in the treatment of ER-positive breast cancer contributed by cholesterol biosynthesis.

Introduction: Disease-modifying anti rheumatic drugs (DMARDs) provide the mainstay for the treatment of rheumatoid arthritis (RA). Adverse effects (AEs) in DMARDs among RA patients are usually related with methotrexate (MTX) use, the common conventional DMARDs. Genetic variant such as single nucleotide polymorphism (SNP) in gene transcribing dihydrofolate reductase (DHFR) (i.e, 829C>T, rs12517451) has been correlated with drug AEs in MTX-treated RA. The prevalence of the DHFR rs12517451 SNP has been reported in other populations, but not in Malaysian. The aim of this study was to determine the prevalence of the DHFR rs12517451 SNP and its association with drug AEs among MTX-treated RA patients from Kelantan, Malaysia. Methods: A total of 78 RA patients receiving MTX (alone or in combination) were included in this study. Based on evidence of clinically perceived drug AEs in MTX-treated RA patients, 33 and 45 samples were assigned as cases and controls, respectively. The genotype of the patients was determined using the polymerase chain reaction-restriction fragment length polymorphism method and validated by sequencing analysis. Results: Minor allele frequency (MAF) for DHFR rs12517451 in cases and controls were 28.8% and 32.2% but there was no significant difference (p=0.727) for the possession of the minor allele T between the two groups. The most reported AEs among cases were haematological effects, gastrointestinal toxicity, and skin problems resulting in 21% withdrawal of MTX. Conclusion: We did not find significant association of the DHFR rs12517451 with drug AEs in MTX-treated RA patients. Our findings warrant replication in a larger patient cohort.