Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Brunetti, Oronzo; Gaspar, António; Licchetta, Antonella; Longo, Vito; Calabrese, Angela; Argentiero, Antonella; Delcuratolo, Sabina; Solimando, Antonio Giovanni; Casadei-Gardini, Andrea; Silvestris, Nicola

doi:10.20944/preprints201909.0071.v1

Cited by 29 publications

(15 citation statements)

References 61 publications

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“…Drug therapy for HCC includes targeted drug therapy such as sorafenib, chemotherapy such as doxorubicin, and immunotherapy such as ICIs/monoclonal antibodies. 5-6,14 However, as HCC patients gradually become resistant to drugs, recent studies have tended to evaluate several clinical and biological markers and their mechanisms to improve the choice of patients suitable for treatment with these drugs. Numerous studies found that several lncRNAs have been involved in drug resistance in HCC.…”

Section: Discussionmentioning

confidence: 99%

“…2 Sorafenib is a small-molecule oral multi-target tyrosine kinase inhibitor (TKI), which is the gold standard for first-line treatment authorized by U.S. Food and Drug Administration (FDA) for advanced liver cancer, which is difficult to operate on. 5 However, the prognosis of HCC patients treated with sorafenib remains poor due to its side effects and the patients’ increased resistance to the drug. 5,6 Studies have shown that the MAPK pathway and BRAF signaling play a vital role in regulating the proliferation and survival of HCC cells: TKI inhibitors exert their activity on HCC cells that inhibit BRAF signaling, and sorafenib can block the MAPK pathway-mediated signal transduction.…”

Section: Introductionmentioning

confidence: 99%

“…5 However, the prognosis of HCC patients treated with sorafenib remains poor due to its side effects and the patients’ increased resistance to the drug. 5,6 Studies have shown that the MAPK pathway and BRAF signaling play a vital role in regulating the proliferation and survival of HCC cells: TKI inhibitors exert their activity on HCC cells that inhibit BRAF signaling, and sorafenib can block the MAPK pathway-mediated signal transduction. 7 For advanced cancers with poor prognoses, such as HCC, these two signaling pathways can be used to investigate their mechanisms to enhance the success rate of treatment.…”

Section: Introductionmentioning

confidence: 99%

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The prognostic significance of long non-coding RNAs in hepatocellular carcinoma: An updated meta-analysis

et al. 2020

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Background: Recently, many studies have demonstrated that long non-coding RNAs (lncRNAs) are abnormally expressed in hepatocellular carcinoma (HCC) and may serve as a potential molecular biomarker to evaluate the prognosis of hepatocellular carcinoma. Therefore, we accomplished a meta-analysis built on current studies to assess the prognostic value of lncRNAs in hepatocellular carcinoma. Methods: The PubMed database was carefully searched to collect all eligible studies until February 20, 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of the overall survival, relapse-free survival, and progression-free survival were calculated to evaluate the prognostic significance of lncRNAs expression in hepatocellular carcinoma using Stata12.0 software. Heterogeneity, sensitivity analysis, and publication bias were also evaluated. Results: The results showed that the expression level of lncRNAs was significantly correlated with clinical outcomes. Abnormally expressed lncRNAs predicted poor overall survival (HR=2.19, 95% CI: 1.99-2.42, P<0.001; I2=44.7%, P=0.005), relapse-free survival (HR=2.68, 95% CI: 1.74-4.14, P<0.001; I2=0.0%, P=0.763) and progression-free survival of hepatocellular carcinoma patients (HR=2.44, 95% CI: 1.53-3.89, P<0.001; I2=0.0%, P=0.336). Statistical significance was also noted in subgroup meta-analyses that were stratified by follow-up time, cutoff value, and quality score. Moreover, the pooled results indicated that lncRNAs expression was significantly associated with tumor size (HR=1.48, 95% CI: 1.24-1.79), tumor number (HR=1.34, 95% CI: 1.08-1.66), and tumor node metastasis stage (HR=2.10, 95% CI: 1.48-2.99), but not liver cirrhosis and tumor differentiation ( P>0.05). Conclusions: This meta-analysis indicates that lncRNAs are strongly associated with prognosis in hepatocellular carcinoma and may serve as a promising indicator for prognostic evaluation of patients with hepatocellular carcinoma. But larger clinical studies are needed to verify its feasibility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The prognostic significance of long non-coding RNAs in hepatocellular carcinoma: An updated meta-analysis

et al. 2020

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“…Nevertheless, 70–80% of patients cannot benefit from such opportunities because they are diagnosed at an advanced stage and can receive only palliative care. Sorafenib has been the standard choice for a decade in advanced HCC, even if other Tyrosine Kinase Inhibitors (TKIs) as well [4] are characterized by possible primary resistance or acquired resistance [5]. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients [6].…”

Section: Introductionmentioning

confidence: 99%

Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

et al. 2019

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Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70–80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standard care for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results in an alternative first-line treatment for the Chinese clinical oncology guidelines. Moreover, nivolumab and pembrolizumab, two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approved for subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessment of new ICIs-based combinatory approaches.

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“…Nevertheless, 70%-80% of patients cannot benefit from such opportunities because they are diagnosed at an advanced stage and can receive only palliative care. Sorafenib has been the standard choice for a decade in advanced HCC, even if as well as other TKIs as well [4] is characterized by possible primary resistance or acquired resistance [5]. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients [6].…”

Section: Introductionmentioning

confidence: 99%

Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Longo¹,

Brunetti²,

Gaspar³

et al. 2019

Preprint

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Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib has been the standard of care for almost a decade until 2018 when FDA approved an alternative first-line agent namely lenvatinib. Whereas FOLFOX4 results an alternative first-line treatment for the chinese clinical oncology guidelines. In addition to cabozantinib, regorafenib, and ramucirumab, two therapeutics against the PD-L1/PD1 axis have been recently approved for subsequent-line therapy, as nivolumab and pembrolizumab. However, similar to other solid tumors, the response rate of single-agent targeting PD-L1/PD1 axis is low. Therefore a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors, the addition of immune checkpoint inhibitors after resection or during locoregional therapy, immune checkpoint inhibitors in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with an attent evaluation of new ICIs based combinatory approaches.

show abstract

Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Cited by 29 publications

References 61 publications

The prognostic significance of long non-coding RNAs in hepatocellular carcinoma: An updated meta-analysis

The prognostic significance of long non-coding RNAs in hepatocellular carcinoma: An updated meta-analysis

Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

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