Nature Communications published the latest research result of Prof. Jiang Hulin's team entitled “Nanoparticles targeting mutant p53 overcome chemoresistance and tumor recurrence in non-small cell lung cancer”. Bi Yuyang (Master’s degree student) of School of Pharmacy is the first author. Prof. Jiang is the independent corresponding author, and China Pharmaceutical University is the first corresponding affiliation.
Non-small cell lung cancer exhibits significant drug resistance due to elevated level of mutated TP53 (Tumor Protein p53), resulting in poor therapeutic efficacy and low survival rates. However, as a first-line treatment option, cisplatin also possesses the risk of inducing mutations. Accumulation of p53 mutations during cisplatin therapy can further compromise patient survival, highlighting the need for a treatment regimen independent of the p53 pathway.
The group first assessed potential mechanisms of resistance to cisplatin-based progressive chemotherapy noting that increased TP53 mutations heighten cisplatin resistance. To address this, they synthesized Fluplatin, a compound combining cisplatin and fluvastatin, and formulated FP nanoparticles (NPs). These nanoparticles are unaffected by p53 mutations, target the endoplasmic reticulum, degrade mutant p53, and induce endoplasmic reticulum stress, thus exerting potent antitumor effects independently of the p53 pathway. FP NPs slows tumor progression and holds promise for improving the poor prognosis in cases with p53 mutations.
This work was supported by the Key International (Regional) Cooperative Research Program of the National Natural Science Foundation of China and the Key Research and Development Program of the Ministry of Science and Technology, as well as the State Key Laboratory of Natural Medicines.
Paper Link：https://doi.org/10.1038/s41467-024-47080-3
Preparation of FP NPs and its antitumor mechanism
（Source：School of Pharmacy，Written by：Liu Hua, Translated by：Gan Jue）
