Correlation of radiotherapy, targeted therapy, and immunotherapy with hepatocellular carcinoma recurrence

Table 2 The mechanism of action of targeted therapy, efficacy in hepatocellular carcinoma recurrence, main limitations and relevant improvement strategies

Type	Treatment	Mechanism	Efficacy	Limitations	Strategies	Ref.
First-line treatment; Second-line treatment	Sorafenib	Inhibit VEGFR, PDGFR-β, and the RAF/MEK/ERK pathway	Sorafenib significantly improved the median overall survival (10.7 months vs 7.9 months; P < 0.001) and radiographic progression-free survival (5.5 months vs 2.8 months; P < 0.001) in patients with advanced HCC	The use of sorafenib as monotherapy in adjuvant treatment and the prevention of HCC recurrence after surgery has no significant efficacy	TACE + sorafenib/TACE + sorafenib + radiotherapy; Switch to other effective medications	Wilhelm et al[40];Rimassa and Santoro[41];Bruix et al[42];Li et al[43];Jiang et al[44];Peng et al[45];Fan et al[46]
	Lenvatinib	Inhibit VEGFR 1-3, FGFR 1-4, PDGFR-α, RET and KIT	Lenvatinib has a superior ORR compared to sorafenib in HCC; The median overall survival in the lenvatinib group for the treatment of recurrent hepatocellular carcinoma after liver transplantation was significantly longer (15.0 months vs 7.8 months, P = 0.02)	Individual differences and resistance exist	TACE + lenvatinib/pembrolizumab + lenvatinib; Switch to other effective medications	Yamamoto et al[48]; Al-Salama et al[49]; Kudo et al[51]; Magyar et al[52];Peng et al[53];Liang et al[54];Zhang et al[55];Lv et al[56]
Second-line treatment	Regorafenib	Inhibit VEGFR1-3, TIE2, FGFR, PDGFR-β, KIT, RET and p38MAPK/Creb1/Klf4	Regorafenib has demonstrated good anti-tumor activity and effectively prolonged survival in HCC patients who experienced recurrence or progression after sorafenib treatment	Severe toxic side effects with a high incidence	Adopt a stepwise dosing strategy	Eso and Marusawa[58]; Ou et al[59]; Bruix et al[60]; Bruix et al[61]; Finn et al[62]; Bekaii-Saab et al[63]
	Cabozantinib	Inhibit VEGFR1-3, MET and AXL	The phase III clinical trial was positive, with an overall ORR of 4%	The overall efficacy is limited	Cabozantinib + nivolumab; Screening for sensitive patients	Argentiero et al[64]; Abou-Alfa et al[65]; Yang et al[66]

VEGFR: Vascular endothelial growth factor receptor; PDGFR: Platelet-derived growth factor receptor; FGFR: Fibroblast growth factor receptor; TIE2: Angiopoietin-1 receptor; MAPK: Mitogen-activated protein kinase; ORR: Objective response rate; HCC: Hepatocellular carcinoma; TACE: Transarterial chemoembolization.