Molecularly targeting the PI3K-Akt-mTOR pathway can sensitize cancer cells to radiotherapy and chemotherapy

Cellular & Molecular Biology Letters

Ziwen Wang²  Yujung Huang¹  Jiqiang Zhang³ 

[1] Department of Environmental Hygiene, College of Military Preventive Medicine, Third Military Medical University, Chongqing, China$$;Department of Preventive Medicine, College of Military Preventive Medicine, Third Military Medical University, Chongqing, China$$;Department of Neurobiology, Third Military Medical University, Chongqing, China$$

关键词: PI3K;    Akt;    Target of rapamycin;    Ribonucleotide reductase;    p53;    FANCD2;    Drug resistance;    DNA damage response;    Chemotherapy;    Radiotherapy;    ATM;   

DOI  :  10.2478/s11658-014-0191-7

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

Radiotherapy and chemotherapeutic agents that damage DNA are the current major non-surgical means of treating cancer. However, many patients develop resistances to chemotherapy drugs in their later lives. The PI3K and Ras signaling pathways are deregulated in most cancers, so molecularly targeting PI3K-Akt or Ras-MAPK signaling sensitizes many cancer types to radiotherapy and chemotherapy, but the underlying molecular mechanisms have yet to be determined. During the multi-step processes of tumorigenesis, cancer cells gain the capability to disrupt the cell cycle checkpoint and increase the activity of CDK4/6 by disrupting the PI3K, Ras, p53, and Rb signaling circuits. Recent advances have demonstrated that PI3K-Akt-mTOR signaling controls FANCD2 and ribonucleotide reductase (RNR). FANCD2 plays an important role in the resistance of cells to DNA damage agents and the activation of DNA damage checkpoints, while RNR is critical for the completion of DNA replication and repair in response to DNA damage and replication stress. Regulation of FANCD2 and RNR suggests that cancer cells depend on PI3K-Akt-mTOR signaling for survival in response to DNA damage, indicating that the PI3K-AktmTOR pathway promotes resistance to chemotherapy and radiotherapy by enhancing DNA damage repair.

【 授权许可】

Unknown