Second-line treatment options in hepatocellular carcinoma

Marino, Donatella; Zichi, Clizia; Audisio, Marco; Sperti, Elisa; Maïo, Massimo Di

doi:10.7573/dic.212577

Cited by 32 publications

(27 citation statements)

References 60 publications

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“…Second-line therapies for advanced HCC that are intolerant to first-line treatment include Regorafenib, Cabozantinib, Sunitinib, Linifanib, Brivanib, Tivantinib, Donafenib, etc. which target tyrosine kinases, HGF-MET axis, and related pathways ( 108 ). Though many of these newer therapies show improved survival with robust and durable responses, development of drug resistance, severe adverse events, and cytostatic properties limit therapeutic benefits and patient acceptability.…”

Section: Targeting Immunity In Hcc: Current Strategies Limitations mentioning

confidence: 99%

“Complimenting the Complement”: Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma

et al. 2021

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Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic necroinflammation, progressive fibrosis, and cirrhosis as precedent events along with dysregulated innate and adaptive immune responses. Central to these immunological networks is the complement cascade (CC), a fundamental defense system inherent to the liver which tightly regulates humoral and cellular responses to noxious stimuli. Importantly, the liver is the primary source for biosynthesis of >80% of complement components and expresses a variety of complement receptors. Recent studies implicate the complement system in liver inflammation, abnormal regenerative responses, fibrosis, carcinogenesis, and development of HCC. Although complement activation differentially promotes immunosuppressive, stimulant, and angiogenic microenvironments conducive to HCC development, it remains under-investigated. Here, we review derangement of specific complement proteins in HCC in the context of altered complement regulatory factors, immune-activating components, and their implications in disease pathogenesis. We also summarize how complement molecules regulate cancer stem cells (CSCs), interact with complement-coagulation cascades, and provide therapeutic opportunities for targeted intervention in HCC.

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Section: Targeting Immunity In Hcc: Current Strategies Limitations mentioning

confidence: 99%

“Complimenting the Complement”: Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma

et al. 2021

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“…This drug developed by Bayer was FDA-approved in June 2017 as a second-line oral drug for unresectable HCC [ 56 ]. Comparing regorafenib and sorafenib effects, the first drug has shown more effectiveness in inhibiting tyrosine kinases and phosphatases, with a better drug tolerance profile in HCC patients.…”

Section: Pharmacological Systemic Drugs In Hccmentioning

confidence: 99%

Liver Cancer: Therapeutic Challenges and the Importance of Experimental Models

Galicia-Moreno

Silva-Gomez

Lucano-Landeros

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

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Liver cancer is one of the main causes of death related to cancer worldwide; its etiology is related with infections by C or B hepatitis virus, alcohol consumption, smoking, obesity, nonalcoholic fatty liver disease, diabetes, and iron overload, among other causes. Several kinds of primary liver cancer occur, but we will focus on hepatocellular carcinoma (HCC). Numerous cellular signaling pathways are implicated in hepatocarcinogenesis, including YAP-HIPPO, Wnt-β-catenin, and nuclear factor-κB (NF-κB); these in turn are considered novel therapeutic targets. In this review, the role of lipid metabolism regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in the development of HCC will also be discussed. Moreover, recent evidence has been obtained regarding the participation of epigenetic changes such as acetylation and methylation of histones and DNA methylation in the development of HCC. In this review, we provide detailed and current information about these topics. Experimental models represent useful tools for studying the different stages of liver cancer and help to develop new pharmacologic treatments. Each model in vivo and in vitro has several characteristics and advantages to offer for the study of this disease. Finally, the main therapies approved for the treatment of HCC patients, first- and second-line therapies, are described in this review. We also describe a novel option, pirfenidone, which due to its pharmacological properties could be considered in the future as a therapeutic option for HCC treatment.

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“…Immunotherapeutic agents may be promising for combination therapy with sorafenib and other antiangiogenetic drugs, since the major toxicity profiles of TKIs and immunotherapeutic drugs do not overlap. Results from phase-1 and -2 studies are already available and show potential benefit compared to anti-PD1 monotherapy [30,31]. In addition, the adverse events in these combination treatments were manageable.…”

Section: Ongoing Trials and The Future Of Liver Cancer Treatmentmentioning

confidence: 99%

Systemic therapy in advanced-stage hepatocellular carcinoma

Graziadei

2020

memo

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Hepatocellular carcinoma (HCC) is a complex disease, since both choice of treatment and prognosis depend not only on tumor-specific but also on liver-related characteristics. Therefore, a multidisciplinary approach in specialized clinics is required for the optimal management of HCC patients. Almost half of patients present with advanced-stage tumor with no curative therapeutic options. According to international guidelines, palliative systemic therapy is recommended in these patients. The multikinase inhibitor sorafenib was the first drug to show antitumor efficacy and was the only approved treatment for almost a decade, as several other agents failed to improve patient survival. In recent years, treatment practices have changed with lenvatinib as another first-line treatment choice and regorafenib, cabozantinib, and ramucirumab as second-line therapeutic options. However, only patients with preserved liver function (Child-Pugh-Turcotte [CPT]-A) were enrolled in these studies and are consequently suitable for these drugs. After promising phase-1 and phase-2 studies, subsequent phase-3 trials evaluating the immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab have failed to demonstrate a significant improvement in patient survival. Ongoing trials are evaluating the combination of ICIs with tyrosine kinase inhibitors or vascular endothelial growth factor (VEGF) inhibitors. Recently, in a phase-3 trial, the combination therapy atezolizumab and bevacizumab led to a significantly improved overall survival compared to sorafenib in the first-line setting. Further

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Second-line treatment options in hepatocellular carcinoma

Cited by 32 publications

References 60 publications

“Complimenting the Complement”: Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma

“Complimenting the Complement”: Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma

Liver Cancer: Therapeutic Challenges and the Importance of Experimental Models

Systemic therapy in advanced-stage hepatocellular carcinoma

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