Involvement of DNA Damage Response Pathways in Hepatocellular Carcinoma

Table 3

Summary of the involvement of the DDR pathways in potential therapy resistance in HCC.

Protein	DNA repair pathway	Underlying effects	Reference
Chk-1	HR	Shh ligand abolished RT-induced phosphorylation of Chk-1 as well as impairing the repair of DNA DSB, which results in HCC cells, HA22T, and Sk-Hep1, resistant to radiotherapy.	[232]
Chk-2		UCN-01 promotes the cytotoxicity of paclitaxel in paclitaxel resistant HCC cells (SNU449, SNU398, SUN368, SNU354, and HepG2 cells) via inhibiting activity of Chk-2.	[233, 259]
ECCR1	NER	HCC patients with increased nuclear staining of ERCC1 are positively correlated with resistance of cisplatin treatment.	[236]
XPC		Increased XPC is associated with liver fibrogenesis and cancer and could be related to the well-recognized resistance of HCC to chemotherapeutics.	[135]
ATM	HR or NHEJ	Small molecular inhibitor, CGK733, which targets kinase activity of ATM can obviously reverse HBV-positive HCC cells,	[147]
		KU55933, ATM inhibitor cotreat with sorafenib, multikinase inhibitor, shows synthetic cytotoxicity to HepG2 cells.	[148]