Loading...
Please wait, while we are loading the content...
Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Zhao, Yuhua Liu, Hao Liu, Zixing Ding, Yan Ledoux, Susan P. Wilson, Glenn Lloy. Voellmy, Richard Lin, Yin C. Lin, Wensheng Nahta, Rita Liu, Bolin Fodstad, Oystein Chen, Jieqing Wu, Yun Price, Janet E. Tan, Ming Zhen |
| Copyright Year | 2011 |
| Abstract | Trastuzumab shows remarkable efficacy in treatment of ErbB2-positive breast cancers when used alone or in combination with other chemotherapeutics. However, acquired resistance develops in most treated patients, necessitating alternate treatment strategies. Increased aerobic glycolysis is a hallmark of cancer and inhibition of glycolysis may offer a promising strategy to preferentially kill cancer cells. In this study, we investigated the antitumor effects of trastuzumab in combination with glycolysis inhibitors in ErbB2-positive breast cancer. We found that trastuzumab inhibits glycolysis via downregulation of heat shock factor 1 (HSF1) and lactate dehydrogenase A (LDH-A) in ErbB2-positive cancer cells, resulting in tumor growth inhibition. Moreover, increased glycolysis via HSF1 and LDH-A contributes to trastuzumab resistance. Importantly, we found that combining trastuzumab with glycolysis inhibition synergistically inhibited trastuzumab-sensitive and -resistant breast cancers in vitro and in vivo, due to more efficient inhibition of glycolysis. Taken together, our findings show how glycolysis inhibition can dramatically enhance the therapeutic efficacy of trastuzumab in ErbB2-positive breast cancers, potentially useful as a strategy to overcome trastuzumab resistance. |
| Starting Page | 237 |
| Ending Page | 241 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/early/2011/04/19/0008-5472.CAN-11-0127.full.pdf |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/71/13/4585.full.pdf |
| PubMed reference number | 21498634v1 |
| Alternate Webpage(s) | https://doi.org/10.1158/0008-5472.CAN-11-0127 |
| DOI | 10.1158/0008-5472.can-11-0127 |
| Journal | Cancer research |
| Volume Number | 71 |
| Issue Number | 13 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Down-Regulation ERBB2 protein, human F Factor Glycolysis Inhibition Heat-Shock Response In Vitro [Publication Type] Lactic acid Mammary Neoplasms Patients Shock cancer cell cellular targeting glucose metabolism lactate dehydrogenase A trastuzumab |
| Content Type | Text |
| Resource Type | Article |
