4.8 Article

Augmenting Tumor-Starvation Therapy by Cancer Cell Autophagy Inhibition

期刊

ADVANCED SCIENCE
卷 7, 期 6, 页码 -

出版社

WILEY
DOI: 10.1002/advs.201902847

关键词

autophagy; black phosphorus; glycolysis; nanomedicine; tumor-starvation therapy

资金

  1. National Key R&D Program of China [2016YFA0203700]
  2. National Natural Science Foundation of China [21835007, 51722211, 51672303]
  3. Natural Science Foundation of Shanghai [13ZR1463500]
  4. National Science Foundation for Young Scientists of China [81903178]
  5. Program of Shanghai Academic Research Leader [18XD1404300]
  6. Tongji University School of Medicine

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It was recently recognized that cancer therapeutic efficacy may be greatly compromised by an intrinsic protective mechanism called autophagy, by which cancer cells survive in harsh conditions such as starvation. Here, a synergetic strategy is described for cancer treatment by suppressing such a protective mechanism for augmenting tumor-starvation therapy. The synergetic therapy is achieved by restraining glucose metabolism using an antiglycolytic agent to predispose cancer cells to severe energy deprivation; concurrently the downstream autophagic flux and compensatory energy supplies are blocked by the autophagy inhibitor black phosphorus nanosheet. Cancer cells fail to extract their own nutrient to feed themselves, finally succumbing to therapeutic interventions and starving to death. Both in vitro and in vivo results evidence the cooperative effect between the autophagy inhibitor and antiglycolytic agent, which leads to remarkable synergetic antineoplastic outcome. It is expected that such a combinational approach by concurrently blocking exogenous and endogenous nutrition supplies will be beneficial to the design of effective tumor-specific cancer therapies in the future.

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