Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma
Ontology highlight
ABSTRACT:
SUBMITTER: Wang J
PROVIDER: S-EPMC10867224 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Hepatocellular carcinoma (HCC) is the most common liver tumor and among the deadliest cancers worldwide. Advanced HCC overall survival is meager and has not improved over the last decade despite approval of several tyrosine kinase inhibitors (TKi) for first and second-line treatments. The recent approval of immune checkpoint inhibitors (ICI) has revolutionized HCC palliative care. Unfortunately, the majority of HCC patients fail to respond to these therapies. Here, we elaborate on the immune landscapes of the normal and cirrhotic livers and of the unique HCC tumor microenvironment. We describe the molecular and immunological classifications of HCC, discuss the role of specific immune cell subsets in this cancer, with a focus on myeloid cells and pathways in anti-tumor immunity, tumor promotion and immune evasion. We also describe the challenges and opportunities of immunotherapies in HCC and discuss new avenues based on harnessing the anti-tumor activity of myeloid, NK and γδ T cells, vaccines, chimeric antigen receptors (CAR)-T or -NK cells, oncolytic viruses, and combination therapies.
| S-EPMC8012774 | biostudies-literature
Project description:Cases of hepatocellular carcinoma (HCC) are rapidly rising. This is particularly the case in the Western world, as a result of increasing rates of chronic liver disease, secondary to lifestyle-associated risk factors and the lack of an established screening programme for the general population. Traditionally, radical/curative treatment options for HCC, including liver transplantation and surgical resection are reserved for the minority of patients, presenting with an early stage cancer. For patients with advanced disease, Sorafenib and Lenvatinib were, until recently, the only licensed systemic treatments, and provided only limited survival benefits at the cost of a multitude of potential side effects. Recent scientific advances in the field of cancer immunotherapy have renewed significant interest in advanced HCC, in order to fulfil this apparent area of unmet clinical need. This has led to the success and recent regulatory approval of an Atezolizumab/Bevacizumab combination for the first-line treatment of advanced HCC following results from the IMbrave150 clinical trial in 2019, with further immune checkpoint inhibitors currently undergoing testing in advanced clinical trials. Furthermore, other cancer immunotherapies, including chimeric antigen receptor T-cells, dendritic cell vaccines and oncolytic viruses are also in early stage clinical trials, for the treatment of advanced HCC. This review will summarise the major approaches that have been and are currently in development for the systemic treatment of advanced HCC, their advantages, drawbacks, and predictions of where this revolutionary treatment field will continue to travel for the foreseeable future.
| S-EPMC8817091 | biostudies-literature
Project description:Primary liver cancer is the second leading cause of tumor-related deaths in China, with hepatocellular carcinoma (HCC) accounting for 80%-90% of these. Since there is a lack of symptoms in the early stages of HCC, a large proportion of patients were identified with unresectable HCC when diagnosed. Due to the severe resistance to chemotherapy, patients with advanced HCC were traditionally treated with systematic therapy in the past decades, and the tyrosine kinase inhibitor (TKI) sorafenib has remained the only treatment option for advanced HCC since 2008. Immunotherapies, particularly immune checkpoint inhibitors (ICIs), have shown a strong anti-tumor effect and have been supported by several guidelines recently. ICIs, for example programmed cell death-1 (PD-1) inhibitors such as nivolumab and pembrolizumab, programmed cell death ligand 1 (PD-L1) inhibitors such as atezolizumab, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors such as ipilimumab, the ICI-based combination with TKIs, and VEGF-neutralizing antibody or systematic or local anti-tumor therapies, are being further studied in clinical trials. However, immune-related adverse events (irAEs) including cutaneous toxicity, gastrointestinal toxicity, and hepatotoxicity may lead to the termination of ICI treatment or even threaten patients' lives. This review aims to summarize currently available immunotherapies and introduce the irAEs and their managements in order to provide references for clinical application and further research.
| S-EPMC10070708 | biostudies-literature
Project description: Not available
| S-EPMC10282679 | biostudies-literature
Project description:AimTo demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.MethodsA total of 143 patients (83.1% of the 172 participants in the phase II study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase II trial. Safety parameters and the following efficacy endpoints were investigated: (1) time to recurrence; (2) disease-free survival; and (3) overall survival.ResultsPI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group: (1) the recurrence-free rate increased from 50% to 63%, and (2) time to recurrence at the 36th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate (11 out of 54 patients). Additionally, subgroup analyses of patients with (1) multiple tumors or a single tumor ≥ 2 cm; and (2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage (56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence.ConclusionAdministering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.
| S-EPMC4145780 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE22790: Gene expression after treatment with anti-miR-191 or control GSE22793: miR expression after treatment with anti-miR-191 or control GSE22909: Influence of TCDD onto HCC cell line Refer to individual Series
2011-07-01 | E-GEOD-22910 | biostudies-arrayexpress
Project description:Previous studies have shown that metformin or statins may decrease hepatocellular carcinoma (HCC) in diabetic patients. Accordingly, this article evaluates whether combination therapy may further reduce HCC. Newly diagnosed type 2 diabetes mellitus (DM) patients, excluding those with history of malignancy prior to the date of DM diagnosis, were recruited to a DM cohort. DM patients developed HCC as the cancer cohort and the date for HCC diagnosis as index date. Non-cancer cohort was frequency matched with 4:1 according to age, sex, DM-year, and index date as case group from DM cohort. Patients who were treated with statins showed a 63% decreased risk of HCC (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.27-0.49). Patients who consumed simvastatin, atorvastatin, or rosuvastatin significantly decreased risk for HCC (OR = 0.32, 0.31, and 0.22; 95% CI = 0.18-0.58, 0.19-0.52, and 0.08-0.61, respectively). Metformin combinations with simvastatin, atorvastatin, or rosuvastatin may decrease HCC (OR = 0.30, 0.30, and 0.24; 95% CI = 0.15-0.59, 0.16-0.54, and 0.08-0.70, respectively). The comorbidities for HCC were decreased by consuming simvastatin and atorvastatin (OR = 0.31 and 0.29; 95% CI = 0.14-0.67 and 0.15-0.57, respectively). Only combination therapy of metformin and simvastatin may significantly decreased HCC comorbidities (OR = 0.26; 95% CI = 0.11-0.60) in our study. In Asia, not all metformin combinations with statins may reduce the incidence of HCC and not all of this kind of combination therapy may decrease the HCC comorbidities.
| S-EPMC4616544 | biostudies-other
Project description:A 10-year-old spayed female Pomeranian dog was referred for hepatic mass evaluation. Blood tests revealed mildly elevated alkaline phosphatase activities. Computed tomography revealed a mass with multiple nodules on the right hepatic medial lobe adjacent to the caudal vena cava; histopathology confirmed mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of incomplete resection, adjuvant therapy was recommended. As tumour cells showed PDGFR-α, c-Kit, and FGFR1 overexpression, the anticancer effect of tyrosine kinase inhibitors was evaluated on the cells; toceranib was the most effective and was administered starting with an extra-labelled dose. The dog remained stable for 2.3 years with mild adverse effects. To our knowledge, this is the first successful clinical application of toceranib in a dog with mixed HCC-CC.
| S-EPMC10847815 | biostudies-literature
Project description:Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine et al. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.
| S-EPMC10149944 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a highly aggressive disease that is usually diagnosed at an advanced stage. Advanced HCC has limited treatment options and often has a poor prognosis. For the past decade, tyrosine kinase inhibitors have been the only treatments approved for advanced HCC that have shown overall survival (OS) benefits; however, but their clinical efficacy has been limited. Recent trials have demonstrated promising advancements in survival outcomes through immunotherapy-based treatments, such as combinations of immune checkpoint inhibitors (ICIs) with other ICIs, antiangiogenic drugs, and locoregional therapies. The atezolizumab-bevacizumab and durvalumab-tremelimumab (STRIDE) regimen has significantly improved survival rates as a first-line treatment and has become the new standard of care. Therefore, combined treatments for advanced HCC can result in better treatment outcomes owing to their synergistic effects, which requires a multidisciplinary approach. Ongoing studies are examining other therapeutic innovations that can improve disease control and OS rates. Despite improvements in the treatment of advanced HCC, further studies on the optimal treatment selection and sequences, biomarker identification, combination approaches with other therapies, and development of novel immunotherapy agents are required. This review presents the current treatment options and clinical data of the ICI-based combination immunotherapies for advanced HCC from a multidisciplinary perspective.
| S-EPMC10565553 | biostudies-literature