A Review of Current and Emerging Therapies for Advanced Hepatocellular Carcinoma

Singh, Angelica; Zahid, Sofia; Noginskiy, Ilya; Pak, Timothy; Usta, Soeb; Barsoum, Marina; Khan, Uqba

doi:10.3390/curroncol29090507

Cited by 8 publications

(5 citation statements)

References 63 publications

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“…Sorafenib is currently a first‐line chemotherapeutic drug for treatment of advanced HCC and metastatic colon cancer. 35 However, oral administration of sorafenib is associated with a variety of adverse effects, including diarrhea and fatigue, which can lead to discontinuation of chemotherapy and cardiovascular events, including hypertension. 36 More importantly, patients frequently develop multidrug resistance (MDR) shortly after sorafenib exposure.…”

Section: Discussionmentioning

confidence: 99%

TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway

Shu,

Zhou,

Lei

et al. 2024

Cancer Science

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Liver cancer is the sixth most common cancer and the third leading cause of cancer‐related death globally. Despite efforts being made in last two decades in cancer diagnosis and treatment, the 5‐year survival rate of liver cancer remains extremely low. TRIM21 participates in cancer metabolism, glycolysis, immunity, chemosensitivity and metastasis by targeting various substrates for ubiquitination. TRIM21 serves as a prognosis marker for human hepatocellular carcinoma (HCC), but the mechanism by which TRIM21 regulates HCC tumorigenesis and progression remains elusive. In this study, we demonstrated that TRIM21 protein levels were elevated in human HCC. Elevated TRIM21 expression was associated with HCC progression and poor survival. Knockdown of TRIM21 in HCC cell lines significantly impaired cell growth and metastasis and enhanced sorafenib‐induced toxicity. Mechanistically, we found that knockdown of TRIM21 resulted in cytosolic translocation and inactivation of YAP. At the molecular level, we further identified that TRIM21 interacted and induced ubiquitination of MST1, which resulted in MST1 degradation and YAP activation. Knockdown of MST1 or overexpression of YAP reversed TRIM21 knockdown‐induced impairment of HCC growth and chemosensitivity. Taken together, the current study demonstrates a novel mechanism that regulates the Hippo pathway and reveals TRM21 as a critical factor that promotes growth and chemoresistance in human HCC.

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Section: Discussionmentioning

confidence: 99%

TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway

Shu,

Zhou,

Lei

et al. 2024

Cancer Science

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“…HCC is a global health concern, with the incidence reaching >90,000 cases by 2025 [ 25 , 26 ]. ICD is a modality that is closely associated with tumorigenesis development by recognizing surface antigens that further induce immune cell collections on tumor cells, thereby promoting necrosis through immune cell infiltration [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value and immune landscapes of immunogenic cell death-related lncRNAs in hepatocellular carcinoma

et al. 2023

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Background: Both immunogenic cell death (ICD) and long noncoding RNAs (lncRNAs) are strongly associated with tumor development, but the mechanism of action of ICD-associated lncRNAs in hepatocellular carcinoma (HCC) remains unclear.  Methods: We collected data from 365 HCC patients from The Cancer Genome Atlas (TCGA) database. We formulated a prognostic signature of ICD-associated lncRNAs and a nomogram to predict prognosis. To explore the potential mechanisms and provide clinical guidance, survival analysis, enrichment analysis, tumor microenvironment analysis, tumor mutation burden, and drug sensitivity prediction were conducted based on the subgroups obtained from the risk score.</p>  Results: A prognostic signature of 7 ICD-associated lncRNAs was constructed. Kaplan‒Meier (K‒M) survival curves showed a more unfavorable outcome in high-risk patients. The nomogram had a higher predictive value than the nomogram constructed without the risk model. Enrichment analysis confirmed that risk lncRNAs were closely associated with cell proliferation and mitosis. Most of the immune checkpoints currently used in therapy (e.g., PDCD1, CTLA4) appeared to be elevated in high-risk patients. Tumor microenvironment analysis showed differential expression of lymphocytes (including natural killer cells, regulatory T cells, etc.) in the high-risk group. The tumor mutation burden (TMB) had a higher incidence of mutations in the high-risk group (p=0.004). Chemotherapy drug sensitivity prediction provides effective guidelines for individual therapy. RT‒qPCR of human HCC tissues verified the accuracy of the model.</p>  Conclusion: We constructed an effective prognostic signature for patients with HCC using seven ICD-lncRNAs, which provides guidance for the prognostic assessment and personalized treatment of patients.</p>

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“…Systemic therapy is typically reserved for tumours with large vascular invasion, those that can no longer be controlled with local therapy approaches or those with extrahepatic metastases. Unlike ICC, cytotoxic chemotherapy has had little benefit and systemic treatment is either a variety of tyrosine kinase inhibitors (TKIs) such as sorafenib or lenvatinib, or IO agents in combination with targeted therapy 21 22. First-line systemic therapy preferred regimens are either the combination of atezolizumab and bevacizumab per the IMBrave 150 study23 or tremelimumab plus durvalumab, after the results of the HIMALAYA trial demonstrated improved OS when compared with sorafenib 24…”

Section: Introductionmentioning

confidence: 99%

Efficacy of dual checkpoint inhibitors in a patient with a mixed hepatocellular cholangiocarcinoma

Sucre,

Bullock,

Peters

2024

BMJ Case Rep

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A woman in her 60s was diagnosed with a metastatic, unresectable rare histological type of liver cancer; combined hepatocellular cholangiocarcinoma. She had palliative chemotherapy, initially with gemcitabine and cisplatin, and then with oxaliplatin, L-folinic acid and fluorouracil. Both treatment strategies demonstrated disease progression, and somatic mutation profiling revealed no actionable mutations. The patient was started on immuno-oncology (IO) with nivolumab and ipilimumab, followed by maintenance nivolumab. She has achieved a sustained ongoing partial response since the start of this therapy for at least 12 months. The outcome in this patient is in keeping with the growing evidence of the role that IO agents have in metastatic biliary tract cancer and also serves to highlight their importance in mixed histology liver tumours.

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A Review of Current and Emerging Therapies for Advanced Hepatocellular Carcinoma

Cited by 8 publications

References 63 publications

TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway

TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway

Prognostic value and immune landscapes of immunogenic cell death-related lncRNAs in hepatocellular carcinoma

Efficacy of dual checkpoint inhibitors in a patient with a mixed hepatocellular cholangiocarcinoma

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