Prospect of the use of checkpoint inhibitors in hepatocellular cancer treatments

Raufi, Ali; Tirona, Maria Tria

doi:10.2147/cmar.s111673

Cited by 14 publications

(11 citation statements)

References 71 publications

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“…These higher rates of Grade 3‐4 adverse events likely reflect additive effects of tissue autoantigen release as a result of tumour infiltration and/or viral damage in conjunction with ICI‐induced increase of autoreactive T cell activity. There have been a growing number of published studies designed to determine the effects of ICIs for the treatment of HCC . In one clinical study, HCC patients undergoing CTLA‐4 blockade with tremelimumab who were infected with HCV demonstrated a relatively good liver adverse event profile with only transient elevations of serum aminotransferases after the first dose of therapy …”

Section: Clinical Trials Of Icis: Results Of Risk For Hepatotoxicitymentioning

confidence: 99%

“…There have been a growing number of published studies designed to determine the effects of ICIs for the treatment of HCC. [59][60][61][62][63][64] In one clinical study, HCC patients undergoing CTLA-4 blockade with tremelimumab who were infected with HCV demonstrated a relatively good liver adverse event profile with only transient elevations of serum aminotransferases after the first dose of therapy. 65…”

Section: Studies With Single-agent Ici Treatment Protocolsmentioning

confidence: 99%

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Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents

Suzman

Pelosof

Rosenberg

et al. 2018

Liver International

184

151

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Immune checkpoint inhibitors (ICIs) block CTLA-4, PD-1 and PD-L1, or other molecules that control antitumour activities of lymphocytes. These products are associated with a broad array of immune-related toxicities affecting a variety of organs, including the liver. ICI-associated immune-mediated hepatitis (IMH) ranges in severity between mild and life-threatening and is marked by findings that bear both similarities as well as differences with idiopathic autoimmune hepatitis. Hepatotoxic events are often detected in clinical trials of ICIs that are powered for efficacy. Risk levels for ICI-induced liver injury may be impacted by the specific checkpoint molecule targeted for treatment, the ICI dose levels, and the presence of a pre-existing autoimmune diathesis, chronic infection or tumour cells which infiltrate the liver parenchyma. When patients develop liver injury during ICI treatment, a prompt assessment of the cause of injury, in conjunction with the application of measures to optimally manage the adverse event, should be made. Strategies to manage the risk of IMH include the performance of pretreatment liver tests with regular monitoring during and after ICI treatment and patient education. Using Common Terminology Criteria for Adverse Events developed at the National Cancer Institute to measure the severity level of liver injury, recommended actions may include continued ICI treatment with close patient monitoring, ICI treatment suspension or discontinuation and/or administration of corticosteroids or, when necessary, a non-steroidal immunosuppressive agent. The elucidation of reliable predictors of tumour-specific ICI treatment responses, as well as an increased susceptibility for clinically serious immune-related adverse events, would help optimize treatment decisions for individual patients.

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Section: Clinical Trials Of Icis: Results Of Risk For Hepatotoxicitymentioning

confidence: 99%

Section: Studies With Single-agent Ici Treatment Protocolsmentioning

confidence: 99%

Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents

Suzman

Pelosof

Rosenberg

et al. 2018

Liver International

184

151

View full text Add to dashboard Cite

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“…Overexpression of these checkpoints may lead to cytotoxic T cell exhaustion and a state of immune tolerance to HCC cells. Co-culture studies have demonstrated that PDL-1 or PD-1 blockade through monoclonal antibodies resulted in cytotoxic T cell recovery and improved effector responses (46).…”

Section: Immune Cellsmentioning

confidence: 99%

How does the tumor microenvironment play a role in hepatobiliary tumors?

Kamil¹,

Rowe²

2018

J. Gastrointest. Oncol.

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The tumor microenvironment (TME) is defined as the structural and dynamic network of cellular and non-cellular interactions between malignant cells and the surrounding non-malignant matrix. Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are two of the most challenging gastrointestinal malignancies. Despite clinical advancements in understanding tumor biology and growth of the chemotherapeutic industry, there have been no corresponding improvements in prognosis and overall survival of HCC and PDAC. Both of these cancers have a very intimate relationship with their surrounding environment; the TME is thought to actively participate in initiating and sustaining these malignancies. Individual TME constituents play a vital role in chemoresistance and recurrence after surgery and have been established as independent prognostic factors. This review article will highlight the diverse structural components, key signaling pathways, and extracellular matrices of HCC and PDAC and discuss their crosstalk with tumor cells to promote growth and metastasis. The article will also summarize the latest laboratory and clinical research based on therapeutic targets identified within the TME of both HCC and PDAC.

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“…Moreover, high daily doses (over 800 mg) result in a range of side effects and heavy financial burden. 11 Our aim is to develop novel approaches for increasing the efficacy and safety of molecular targeted agents.…”

Section: Introductionmentioning

confidence: 99%

A novel long-sustaining system of apatinib for long-term inhibition of the proliferation of hepatocellular carcinoma cells

Wang

Tang

2018

OTT

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BackgroundApatinib is a newly approved antitumor drug (molecular targeted agent/small molecular kinase inhibitor) for advanced hepatocellular carcinoma (HCC) treatment. However, current oral administration of apatinib could induce the even distribution of drugs in the body and cause the concentration of apatinib in the HCC location to be limited or insufficient. Therefore, it is urgent to develop novel formulations of apatinib to improve its efficiency.Materials and methodsApatinib was prepared to form a stable and even dispersion with cyclodextrin (a clathrate complex/inclusion complex named Apa-Cyc). A temperature-sensitive phase-change hydrogel of apatinib (named Apa-Gel) was prepared using apatinib–cyclodextrin and poloxamer 407. Apa-Gel was injected into HCC tissues in nude mice to examine the long-term antitumor effect.ResultsApa-Gel can transform from liquid to hydrogel at near body temperature and maintain slow release of apatinib in HCC tumor tissues. When injected subcutaneously, one-time administration of Apa-Gel has a long-acting antitumor effect on the subcutaneous growth or epithelial–mesenchymal transition process of HCC cells.ConclusionThis novel slow-releasing system allows apatinib to be released effectively on the long term and facilitates tissue attachment, thereby preserving the efficiency of apatinib over the long term.

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Prospect of the use of checkpoint inhibitors in hepatocellular cancer treatments

Cited by 14 publications

References 71 publications

Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents

Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents

How does the tumor microenvironment play a role in hepatobiliary tumors?

A novel long-sustaining system of apatinib for long-term inhibition of the proliferation of hepatocellular carcinoma cells

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