lucidating mechanisms of drug resistance is key for overcoming resistance, guiding drug design, and enabling accurate resistance prediction. Recently, disease metabolic reprogramming has emerged as a novel mechanism of resistance, which enables disease cells to adapt to therapeutic resistance by altering energy production pathways, cellular signaling, and biosynthesis processes. Moreover, protein structure alterations also play a pivotal role in resistance study, facilitating mechanistic understanding, and structure-based target discovery. In other words, integrating these recently accumulated critical data is essential for enriching the landscape of drug resistance data. Therefore, in this study, DRESIS was a significant update by providing (i) 236 molecules that drive metabolic reprogramming and confer resistance to 168 drugs, together with a detailed mechanism, (ii) 2228 protein structural variants implicated in resistance to 671 drugs across 238 diseases, and (iii) greatly expanded landscapes of drug resistance information, now featuring 398 newly added key drug-resistant molecules, 356 drugs with the latest published resistance mechanisms, and 81 new drug-resistant disease categories. All in all, DRESIS 2.0 is expected to serve as a valuable resource for the scientific community and provide important support in tackling the global challenge of drug resistance, which is now publicly accessible at https://idrblab.org/dresis/
