2022.01.14 Zhang Zhe's research results were published in the authoritative academic journal EMBO Mol Med

On January 14, 2022, our student Zhang Zhe published a research paper entitled "Inhibition of NPC1L1 disrupts adaptive responses of drug-tolerant persister cells to chemotherapy" in the international authoritative academic journal EMBO Molecular Medicine (impact factor 12.1). Zhang Zhe is the first author of the paper, and the joint first authors are Qin Siyuan and Dr. Chen Yan. Professor Wei Xiawei, State Key Laboratory of Biotherapeutics of Sichuan University, Professor Huang Canhua, my supervisor, and Associate Professor Chen Haining, Department of Gastrointestinal Surgery, West China Hospital, Sichuan University are the co-corresponding authors of the paper. In addition, this work has also received strong support from Academician Wei Yuquan, Director of the State Key Laboratory of Biotherapy at Sichuan University, Associate Professor Lei Yunlong of Chongqing Medical University, and researcher Liu Rui of the West China School of Stomatology of Sichuan University.

Unlike tumor resistance, which develops through genetic mutation, the small cluster of tumor cells remaining after treatment, known as DTP cells, evades treatment through non-genetic resistance mechanisms. Tumor cells that enter the DTP state are highly plastic, survive under treatment stress and combine stem cell characteristics, while tending to oxidative phosphorylation-dependent metabolic transitions. More importantly, they precisely regulate the intracellular redox signaling network, which defends against metabolic reprogramming and oxidative stress caused by tumor treatment by activating a powerful antioxidant defense system. Currently, DTP cells are now considered to be the "seeds" that promote the evolution of traditional genetic resistance and are an important driver of cancer drug resistance relapse. Therefore, exploring the specific role of persistent tolerance in current tumor treatment and elucidating how DTP cells possess strong antioxidant capacity are of great significance for overcoming tumor resistance and delaying tumor recurrence.

We use redox signaling as a starting point to elucidate the cross-dialogue mechanism between steroid lipid transporter NPC1L1-mediated antioxidant modulation and DTP status, and propose a new strategy for treating multidrug-resistant cancer cells and preventing tumor recurrence.