Systemic therapy for advanced hepatocellular carcinoma: an update

Desai, J.; Ochoa, Sebastian; Prins, Petra; He, Aiwu Ruth

doi:10.21037/jgo.2017.02.01

Cited by 57 publications

(51 citation statements)

References 60 publications

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“…Traditional chemotherapy has a limited effect on HCC, especially in advanced phases. Many studies are evaluating the combination of sorafenib with TACE, or with other chemotherapeutic agents already in use for the treatment of other malignancies, or with other molecules that target cell proliferation or angiogenesis [34]. Other possible strategies, currently under evaluation for HCC, include immunotherapy using mainly checkpoint inhibitors that interfere with CTLA-4 or PD-1 pathways [34].…”

Section: Discussionmentioning

confidence: 99%

Impaired Anti-Tumor T cell Response in Hepatocellular Carcinoma

Chaoul

Mancarella

Lupo

et al. 2020

Cancers

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Different subsets of lymphocytes have the capacity to promote or counteract the progression of solid cancers, including hepatocellular carcinoma (HCC). Therefore, to determine the infiltrative ability and functional status of major immune cell subtypes into tumor may lead to novel insights from the perspective of immunotherapy. After obtaining single cell suspensions from freshly collected specimens of HCC tumor, along with paired peritumor tissues and peripheral blood mononuclear cells (PBMCs) from 14 patients, we flow-cytometrically identified and quantified the relative frequencies of lymphocyte subsets within the tissues of origin. We found that the recruitment in the tumor of cytotoxic cells, namely the terminally differentiated CD4+ and CD8+ T cells (TEFF), is impaired, whereas the effector memory CD4+ T cells (TEM) are more attracted in this site. Concerning the other subsets, the frequency of NK CD56hi and NKT CD56hi cells infiltration in the tumor is increased, whereas that of NKT CD56low is reduced. Although CD4+ and CD8+ T cells settled in the tumor show a higher degree of activation than the circulating counterpart, they occur with a more exhausted phenotype. Overall, these data demonstrate the prevalently immunosuppressive nature of HCC microenvironment, and prompt us to search for strategies to enhance the activity of anti-tumor immune cell subsets.

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Section: Discussionmentioning

confidence: 99%

Impaired Anti-Tumor T cell Response in Hepatocellular Carcinoma

Chaoul

Mancarella

Lupo

et al. 2020

Cancers

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“…Recurrence of HCC in remaining parts of the liver, as well as development of extrahepatic distant metastases, is a common and difficult clinical problem. A broad spectrum of drug agents, including immunotherapy approaches, have been or are currently under investigation for the treatment of advanced HCC . Additive and possible synergistic combinations of local and systemic therapies may yield the best outcomes for patients with advanced HCC or those at risk for progression to advanced HCC …”

Section: Future Directionsmentioning

confidence: 99%

“…A broad spectrum of drug agents, including immunotherapy approaches, have been or are currently under investigation for the treatment of advanced HCC. (62) Additive and possible synergistic combinations of local and systemic therapies may yield the best outcomes for patients with advanced HCC or those at risk for progression to advanced HCC. (28,63,64) In conclusion, SABR is one of the most recent additions to the portfolio of local therapies for HCC and other types of liver tumors.…”

Section: Future Directionsmentioning

confidence: 99%

Stereotactic ablative radiotherapy for hepatocellular carcinoma: History, current status, and opportunities

Meyer¹,

Singal

2018

Liver Transpl

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A variety of surgical and other local-regional approaches to the management of hepatocellular carcinoma (HCC) are in clinical use. External beam radiation therapy is a relative newcomer to the portfolio of treatment options. Advances in planning and delivery of radiation therapy, developing in parallel with and inspiring changing paradigms of tumor management in the field of radiation oncology, have led to growing interest in radiation therapy as a viable treatment option for HCC as well as other liver tumors. In this review, we discuss these advances, current trends in liver radiotherapy, as well as avenues of future clinical and basic research. Liver Transplantation 24 420-427 2018 AASLD.

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“…4 ECM degradation by extracellular proteinases contributes to the progress of tumor cell invasion and metastasis. 5 Among these proteolytic proteinase systems, the urokinase plasminogen activator (uPA) plays a critical role in degrading the ECM, thereby allowing metastatic cells to access the vasculature, invade and migrate into the target organ, and thereby result in tumor metastasis. 6,7 The mitogen-activated protein kinase (MAPK) surperfamily members are associated with increased migration, invasion, proliferation, survival, and apoptosis, thus playing different roles in cellular responses.…”

Section: Migration and Invasion Of Cancer Cells And The Related Degramentioning

confidence: 99%

“…First, the cells gain the ability to migrate and invade other tissues; second, they destroy their intercellular relationships; third, the ECM is lysed; and fourth, there is an increase in the adhesive ability between the cells and ECM . ECM degradation by extracellular proteinases contributes to the progress of tumor cell invasion and metastasis . Among these proteolytic proteinase systems, the urokinase plasminogen activator (uPA) plays a critical role in degrading the ECM, thereby allowing metastatic cells to access the vasculature, invade and migrate into the target organ, and thereby result in tumor metastasis .…”

Section: Introductionmentioning

confidence: 99%

Synergistic antimetastatic effect of cotreatment with licochalcone A and sorafenib on human hepatocellular carcinoma cells through the inactivation of MKK4/JNK and uPA expression

Chiu

et al. 2018

Environmental Toxicology

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To improve the clinical outcome of tumor chemotherapy, more effective combination treatments against tumor metastasis and recurrence are required. Licochalcone A (LicA) is the root of Glycyrrhiza inflata and has been reported to possess anti-inflammatory, antimicrobial, and antitumor effects. Sorafenib (Sor), a multikinase inhibitor, is used to treat patients with solid tumors such as advanced hepatocellular carcinoma (HCC). However, the synergistic effects of LicA and Sor on the metastasis of human HCC cells have not been reported. We found that LicA and Sor did not have cytotoxic effects or arrest growth in human SK-Hep-1 and Huh-7 cells. In addition, treatment with LicA or Sor alone inhibited migration and invasion in human SK-Hep-1 and Huh-7 HCC cells. Furthermore, cotreatment with LicA and Sor synergistically inhibited the migration and invasion of HCC cells and significantly inhibited uPA protein expression. Notably, cotreatment of LicA and Sor synergistically and significantly downregulated MKK4-JNK expression. Through tail vein injection in nude mice, the aforementioned cotreatment synergistically suppressed SK-Hep-1 cell-mediated lung metastasis. These findings first revealed the synergistic effects of LicA and Sor cotreatment against human HCC cells, further suggesting that beneficial effects on tumor regression could be confirmed through prospective clinical trials.

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Systemic therapy for advanced hepatocellular carcinoma: an update

Cited by 57 publications

References 60 publications

Impaired Anti-Tumor T cell Response in Hepatocellular Carcinoma

Impaired Anti-Tumor T cell Response in Hepatocellular Carcinoma

Stereotactic ablative radiotherapy for hepatocellular carcinoma: History, current status, and opportunities

Synergistic antimetastatic effect of cotreatment with licochalcone A and sorafenib on human hepatocellular carcinoma cells through the inactivation of MKK4/JNK and uPA expression

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