- Mini Review
Molecularly targeting the PI3K-Akt-mTOR pathway can sensitize cancer cells to radiotherapy and chemotherapy
Cellular & Molecular Biology Letters volume 19, pages 233–242 (2014)
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.
AMP-activated protein kinase
- ATM kinase:
ataxiatelangiectasia mutated kinase
ataxia telangiectasia and Rad3-related
cyclin-dependent kinase 4/6
checkpoint kinase 1
checkpoint kinase 2
Fanconi anemia group D2
Fanconi anemia group I
DNA interstrand crosslinker
insulin-like growth factor binding protein 3
insulin receptor substrate
mitogen-activated protein kinase
mammalian target of rapamycin
nucleotide excision repair
phosphatase/tensin homolog deleted on chromosome 10
Ras-homolog enriched in brain
receptor tyrosine kinase
translesion DNA synthesis
tuberous sclerosis complex-2
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Wang, Z., Huang, Y. & Zhang, J. Molecularly targeting the PI3K-Akt-mTOR pathway can sensitize cancer cells to radiotherapy and chemotherapy. Cell Mol Biol Lett 19, 233–242 (2014). https://doi.org/10.2478/s11658-014-0191-7
- Target of rapamycin
- Ribonucleotide reductase
- Drug resistance
- DNA damage response