Novel antiangiogenic therapies against advanced hepatocellular carcinoma (HCC)

Pazo-Cid, Roberto; Lanzuela, M.; Esquerdo, G.; Pérez-Gracia, José Luis; Antón, A.; Amigo, Gonzalo; Trufero, Javier Martínez; García-Otin, A.L.; Martín-Duque, Pilar

doi:10.1007/s12094-012-0842-y

Cited by 11 publications

(8 citation statements)

References 133 publications

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“…Several clinical trials on second‐line chemotherapy as post‐sorafenib treatment are underway . Even if sorafenib therapy is discontinued owing to progressive HCC, anticancer therapies other than sorafenib therapy could help to elicit potential survival benefits . To successfully undertake post‐sorafenib anticancer therapies, well‐maintained liver function after sorafenib therapy is needed.…”

Section: Discussionmentioning

confidence: 99%

Effect of treatment with branched‐chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma

Takeda

Nishikawa

Iguchi

et al. 2013

Hepatology Research

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Section: Discussionmentioning

confidence: 99%

Effect of treatment with branched‐chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma

Takeda

Nishikawa

Iguchi

et al. 2013

Hepatology Research

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“…Several clinical trials of molecular targeting agents other than sorafenib have been performed. However, no trials to date have shown that any of these agents have superior efficacy compared with sorafenib for the treatment of unresectable HCC . The EASL guidelines recommend sorafenib for unresectable, advanced, Child–Pugh A or B HCC with PS 0–2 and vascular invasion or distant metastasis .…”

Section: Hcc Therapy: Changes For the Last Few Decadesmentioning

confidence: 99%

“…Although sorafenib has a significantly higher survival benefit for patients with advanced HCC, the response to sorafenib remains low and the median OS is only extended by approximately 3 months . Furthermore, predictive factors of responders to sorafenib in patients with HCC have not been well established .…”

Section: Hcc Therapy: Changes For the Last Few Decadesmentioning

confidence: 99%

Treatment for hepatocellular carcinoma in Japan over the last three decades: Our experience and published work review

Osaki

Nishikawa

2014

Hepatology Research

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. In the last few decades, there has been a marked increase in therapeutic options for HCC and epidemiological characteristics at HCC diagnosis have also significantly changed. With these changes and advances in medical technology and surveillance program for detecting earlier stage HCC, survival in patients with HCC has significantly improved. Especially, patients with liver cirrhosis are at high risk of HCC development, and regular surveillance could enable early detection of HCC and curative therapy, with potentially improved clinical outcome. However, unfortunately, only 20% of HCC patients are amenable to curative therapy (liver transplantation, surgical resection or ablative therapies). Locoregional therapies such as radiofrequency ablation, percutaneous ethanol injection, microwave coagulation therapy and transcatheter arterial chemoembolization play a key role in the management of unresectable HCC. Currently, molecular-targeted agents such as sorafenib have emerged as a promising therapy for advanced HCC. The choice of the treatment modality depends on the size of the tumor, tumor location, anatomical considerations, number of tumors present and liver function. Furthermore, new promising therapies such as gene therapy and immunotherapy for HCC have emerged. Approaches to the HCC diagnosis and adequate management for patients with HCC are improving survival. Herein, we review changes of epidemiological characteristics, prognosis and therapies for HCC and refer to current knowledge for this malignancy based on our experience of approximately 4000 HCC cases over the last three decades.

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“…Thus, the maintenance of antiangiogenic treatments even during progression may be justified in order to prevent such rebound effect of tumor neoangiogenesis [8]. …”

Section: Introductionmentioning

confidence: 99%

Evaluation of the impact of transient interruption of antiangiogenic treatment using ultrasound-based techniques in a murine model of hepatocellular carcinoma

et al. 2014

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BackgroundDevelopment of escape pathways from antiangiogenic treatments was reported to be associated with enhanced tumor aggressiveness and rebound effect was suggested after treatment stop. Aim of the study was to evaluate tumor response simulating different conditions of administration of antiangiogenic treatment (transient or definitive treatment stop) in a mouse model of hepatocellular carcinoma.MethodsSubcutaneous tumors were created by inoculating 5×106 Huh7 cells into the right flank of 14 nude mice. When tumor size reached 5–10 mm, mice were divided in 3 groups: group 1 was treated with placebo, group 2 was treated with sorafenib (62 mg/kg via gavage) but temporarily suspended from day +5 to +9, whereas in group 3 sorafenib was definitively stopped at day +5. At day +13 all mice were sacrificed, collecting masses for Western-Blot analyses. Volume was calculated with B-mode ultrasonography at day 0, +5, +9, +11 and +13. VEGFR2-targeted contrast-enhanced ultrasound using BR55 (Bracco Imaging) was performed at day +5 and +13 and elastonosography (Esaote) at day +9 and +11 to assess tumor stiffness.ResultsMedian growth percentage delta at day +13 versus day 0 was 197% (115–329) in group 1, 81% (48–144) in group 2 and 111% (27–167) in group 3. Median growth delta at day +13 with respect to day +5 was 79% (48–127), 37% (−14128) and 81% (15–87) in groups 1, 2 and 3, respectively. Quantification of targeted-CEUS at day +13 showed higher values in group 3 (509 Arbitrary Units AI, range 293–652) than group 1 (275 AI, range 191–494) and group 2 (181 AI, range 63–318) (p = 0.033). Western-Blot analysis demonstrated higher VEGFR2 expression in group 3 with respect to group 1 and 2.ConclusionsA transient interruption of antiangiogenic treatment does not impede restoration of tumor response, while a definitive interruption tends to stimulate a rebound of angiogenesis to higher level than without treatment.

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Novel antiangiogenic therapies against advanced hepatocellular carcinoma (HCC)

Cited by 11 publications

References 133 publications

Effect of treatment with branched‐chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma

Effect of treatment with branched‐chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma

Treatment for hepatocellular carcinoma in Japan over the last three decades: Our experience and published work review

Evaluation of the impact of transient interruption of antiangiogenic treatment using ultrasound-based techniques in a murine model of hepatocellular carcinoma

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