期刊
ONCOTARGET
卷 6, 期 14, 页码 11820-11832出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3689
关键词
tyrosine kinase inhibitors; fasting; MAPK pathway; E2F transcription factors; cell cycle regulation
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [6108]
- Seventh Framework project PANACREAS [256986]
- Compagnia di San Paolo [ROL 689]
- Fondazione Umberto Veronesi
- University of Genoa
Tyrosine kinase inhibitors (TKIs) are now the mainstay of treatment in many types of cancer. However, their benefit is frequently short-lived, mandating the search for safe potentiation strategies. Cycles of fasting enhance the activity of chemo-radiotherapy in preclinical cancer models and dietary approaches based on fasting are currently explored in clinical trials. Whether combining fasting with TKIs is going to be potentially beneficial remains unknown. Here we report that starvation conditions increase the ability of commonly administered TKIs, including erlotinib, gefitinib, lapatinib, crizotinib and regorafenib, to block cancer cell growth, to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway and to strengthen E2F-dependent transcription inhibition. In cancer xenografts models, both TKIs and cycles of fasting slowed tumor growth, but, when combined, these interventions were significantly more effective than either type of treatment alone. In conclusion, cycles of fasting or of specifically designed fasting-mimicking diets should be evaluated in clinical studies as a means to potentiate the activity of TKIs in clinical use.
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