Almost all kinds of cancers treated with cisplatin will develop resistance, and this is often caused by a large amount of DNA repair. Therefore, there is an urgent need to find the acquired loopholes in cisplatin-resistant cancers to determine the undiscovered treatment methods. Here, Liang Xingjie of the National Nanoscience Center, Guo Weisheng of Guangzhou Medical University, and Changjin of Tianjin University have discovered that the cisplatin resistance of cancer cells is at the cost of the increased adaptation cost of intracellular hypoxia. An inspiring strategy to combat tumor drug resistance by taking advantage of the increased intracellular hypoxia when cells develop drug resistance.






Key points of this article:

(1) A hypoxia-amplified DNA repair-inhibiting liposome nanomedicine (HYDRI NM for short) was constructed. The drug consists of platinum (IV) prodrugs as the building block, glucose oxidase (GOx) and hypoxia Activated Tilapamine (TPZ) is formulated as a payload.

(2) In the study of clinically relevant models, including patient-derived organoids and patient-derived xenograft tumors, HYDRI NM can effectively inhibit the growth of cisplatin-resistant tumors.






In summary, this study provides a conceptual clinical proof for the above-mentioned therapies.



references:

Jing Chen, et al. Exploiting the acquired vulnerability of cisplatin-resistant tumors with a hypoxia-amplifying DNA repair–inhibiting (HYDRI) nanomedicine. Sci. Adv., 2021.

DOI: 10.1126/sciadv.abc5267

https://advances.sciencemag.org/content/7/13/eabc5267