Current status and future prospects of chemotherapy for advanced hepatocellular carcinoma

Moriguchi, Michihisa; Umemura, Atsushi; Itoh, Yoshito

doi:10.1007/s12328-016-0670-7

Cited by 30 publications

(22 citation statements)

References 55 publications

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“…Several prospective trials have shown unequivocal clinical activity in melanoma and NSCLC (reviewed in [77]). Many trials are focusing on molecular targeted agents in HCC, but most have ended in failure except sorafenib [102, 103] and even this agent shows only a limited increase in survival of approximately 3 months for advanced HCC [104]. Disappointingly, however, BM is a contraindication for sorafenib [105].…”

Section: Radiotherapymentioning

confidence: 99%

Brain metastases from hepatocellular carcinoma: recent advances and future avenues

Wang

Lin

et al. 2017

Oncotarget

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The incidence of brain metastases from hepatocellular carcinoma (BMHCC) is becoming more frequent than that of the past as a result of prolonged survival of patients with HCC. Compared with brain metastases from other types of cancer, BMHCC tends to exhibit a high incidence of intracerebral hemorrhage (ICH) and poor liver function. Unfortunately, the prognosis is extremely poor for patients with BMHCC owing to the limited treatment selection. Currently, optimal treatment requires multidisciplinary approaches including surgery, whole-brain radiation therapy and stereotactic radiosurgery. Besides these traditional approaches, novel treatments such as target therapy and immunotherapy provide an opportunity to improve the survival of these patients. This review provides an overview of the incidence, characteristics, prognosis, and current and potential future management strategies for BMHCC.

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Section: Radiotherapymentioning

confidence: 99%

Brain metastases from hepatocellular carcinoma: recent advances and future avenues

Wang

Lin

et al. 2017

Oncotarget

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“…Sorafenib, a serine-threonine kinase inhibitor, is currently the only approved systematic drug for anti-HCC. Unfortunately, the efficacy of sorafenib is limited, and some patients are intolerant [3]. Therefore, more effective therapeutic strategies for HCC are needed.…”

Section: Introductionmentioning

confidence: 99%

Sinularin induces DNA damage, G2/M phase arrest, and apoptosis in human hepatocellular carcinoma cells

Chung

Lin

et al. 2017

BMC Complement Altern Med

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BackgroundSinularin isolated from the cultured soft coral Sinularia flexibilis has been reported to exert potent cytotoxic effects against particular types of cancer. This study was carried out to investigate the cytotoxic effects in sinularin-treated human hepatocellular carcinoma cells, HepG2, and to subsequently explore the underlying molecular mechanisms.MethodsTheMTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl- tetrazolium bromide) method was used to evaluate the cytotoxicity of sinularin on HepG2 and Hep3B cell lines. Furthermore, the cell cycle distribution assay, apoptosis assay, and western blot analysis in vitro were used to explore the possible mechanisms of action.ResultsFrom the results of our study, cell viability was obviously inhibited by sinularin in a dose-dependent manner. In addition, our results suggested that sinularin triggered DNA damage and subsequently induced cell cycle G2/M arrest associated with up-regulation of p-ATM (Ser(1981)), p-Chk2 (Tyr(68)), p-cdc2 (Tyr(15)), and p53 coupled with increased expression of downstream proteins p21 and down-regulation of p-cdc25 (Ser(216)). Moreover, the results of the apoptosis assay and western blot analysis indicated that the cytotoxic activity could be related to mitochondrial apoptosis, characterized by decrease of Bcl-2 expression, disruption of mitochondrial membrane potential, and sequential activation of caspases and Poly (ADP-ribose) polymerase (PARP).ConclusionsThis study reveals for the first time the anti-HCC activities of sinularin, the active compound isolated from the cultured soft coral Sinularia flexibilis. We believe that our results warrant further evaluation of sinularin as a new anti-HCC chemotherapeutic agent.

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“…Additionally, they do not effectively control distant metastasis rates. Thus, there is unanimous agreement for the urgent requirement to develop novel, more effective drugs and treatment methods for the clinical treatment of HCC (5,15). One suggested approach is to identify drugs that are derived from natural compounds with anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory mechanism of muscone in liver cancer involves the induction of apoptosis and autophagy

Yang

et al. 2020

Oncol Rep

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Traditionally, musk has been used as an analgesic to treat pain associated with cancer. Hepatocellular carcinoma (HCC) is an aggressive tumor; however, patients with liver cancer that received musk were reported to live longer and have a higher quality of life. Thus, the present study aimed to investigate whether muscone, a macrocyclic compound of musk, demonstrated potential as an anti-liver cancer drug for the non-surgical treatment of advanced liver cancer. Briefly, liver cancer cells were treated with muscone and the rates of cellular apoptosis and autophagy were investigated using staining techniques and western blotting. The underlying molecular mechanisms of muscone were evaluated using high-throughput sequencing and the in vitro effects of muscone were subsequently validated in vivo using a nude mouse model. Muscone increased the rates of apoptosis and autophagy in liver cancer cells; the increase in cellular apoptosis was observed to occur through endoplasmic reticulum stress responses, whereas muscone-induced autophagy was closely associated with the AMP kinase/mTOR complex 1 signaling pathway. These findings were verified in vivo. Notably, sestrin-2 expression levels were also significantly decreased in liver cancer tissues compared with paracancerous tissues. In conclusion, the present study suggests that muscone demonstrates potential as an anticancer drug, and the findings of the present study provide the basis for the development of effective anticancer drugs derived from natural compounds.

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Current status and future prospects of chemotherapy for advanced hepatocellular carcinoma

Cited by 30 publications

References 55 publications

Brain metastases from hepatocellular carcinoma: recent advances and future avenues

Brain metastases from hepatocellular carcinoma: recent advances and future avenues

Sinularin induces DNA damage, G2/M phase arrest, and apoptosis in human hepatocellular carcinoma cells

Inhibitory mechanism of muscone in liver cancer involves the induction of apoptosis and autophagy

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