This study explored the relationship between p53 mutations and drug resistance, particularly resistance to methotrexate (MTX), in rheumatoid arthritis (RA) patients. RA synovial fibroblasts with p53 mutations exhibit not only increased resistance to MTX but also an apoptosis-resistant phenotype, complicating treatment efficacy.
This research highlights the dual role of p53 mutations in promoting both cell survival and migration, suggesting a mechanism by which the aggressive nature of RA is aggravated. A significant finding is the link between prolonged MTX treatment and the emergence of p53 mutations. This observation indicates a need for alternative therapeutic strategies.
In addition, this study revealed celastrol, a compound from a Chinese herbal medicine, as a promising alternative capable of overcoming MTX resistance through a p53-independent pathway. This finding suggests the importance of genetic understanding in RA treatment and the potential of celastrol as an effective therapy in cases where conventional treatments fail due to drug resistance.
C. Qiu et al., “The potential development of drug resistance in rheumatoid arthritis patients identified with p53 mutations,” Genes & Diseases, vol. 10, no. 6, pp. 2252–2255, Nov. 2023, doi:
