Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Combination therapy for advanced hepatocellular carcinoma: do we see the light at the end of the tunnel?

ABSTRACT:

Importance

Combination therapies of anti-PD-1 and anti-angiogenesis regimens are emerging rapidly and exhibit more promising anti-tumor efficacy for advanced hepatocellular carcinoma (HCC), and consistently it is the hotspot in clinical studies.

Objective

To elaborate several issues which are warranted further consideration as more regimens are being investigated in combination therapies.

Evidence review

We searched PubMed, MEDLINE, Cochrane Library and Google Scholar by 2021 February for publications on combination therapies for HCC.

Findings

Several clinical issues are worth reconsidering, such as the evaluation on appropriate primary endpoints in phase III clinical trials as for different practical problems, the translation of surrogate endpoint objective response rate (ORR) benefits into overall survival (OS) benefits, and whether conversion surgery contributes to initial expectations of long-term survival or not. New concepts in novel immunotherapy and targeted therapy in combination with loco-regional therapies may improve overall survival for HCC.

Conclusions and relevance for reviews

Comprehensive understanding of the mechanism of immunotherapy and targeted therapy contributes to better prognosis of advanced HCC and more explorative combination therapies are needed.

SUBMITTER: Zhang T

PROVIDER: S-EPMC8050575 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Immunotherapy in Hepatocellular Carcinoma: Is There a Light at the End of the Tunnel?

Project description:Hepatocellular carcinoma (HCC) is the most common primary liver cancer with dismal prognosis when diagnosed at advanced stages. Surgical resection of the primary tumor or orthotropic liver transplantation serves as a potential curative option. However, this approach is highly dependent on the hepatic reserve and baseline functional status of the patient. Liver directed therapies such as portal vein embolization (PVE), trans-arterial chemoembolization (TACE), and systemic chemotherapy are employed in non-surgical candidates. Sorafenib was the only approved systemic therapeutic agent for almost a decade until the recent approval of lenvatinib by the United States Food and Drug Administration (FDA) as an alternate first-line agent. Regorafenib, nivolumab, pembrolizumab and cabozantinib are approved by the FDA as second-line agents in patients who failed or could not tolerate sorafenib. Ramucirumab was recently FDA approved for the subset of patients that have high alfa-fetoprotein levels (>400 ng/mL). A better understanding of tumorigenesis and encouraging clinical trial results that evaluated immune-checkpoint inhibitors opened doors for immunotherapy in HCC. Immune checkpoint inhibitors have demonstrated a prolonged median overall and progression-free survival in a subset of patients with HCC. On-going translational and clinical research will hopefully provide us with a better understanding of tumor markers, genetic aberrations and other factors that determine the immunotherapy response in HCC. In this review, we sought to summarize the potential role and future directions of immunotherapy in the management of HCC.

| S-EPMC6721326 | biostudies-literature

Combination treatment including targeted therapy for advanced hepatocellular carcinoma.

Project description:Management of advanced hepatocellular carcinoma (HCC), one of the most lethal cancers worldwide, has presented a therapeutic challenge over past decades. Most patients with advanced HCC and a low possibility of surgical resection have limited treatment options and no alternative but to accept local or palliative treatment. In the new era of cancer therapy, increasing numbers of molecular targeted agents (MTAs) have been applied in the treatment of advanced HCC. However, mono-targeted therapy has shown disappointing outcomes in disease control, primarily because of tumor heterogeneity and complex cell signal transduction. Because incapacitation of a single target is insufficient for cancer suppression, combination treatment for targeted therapy has been proposed and experimentally tested in several clinical trials. In this article, we review research studies aimed to enhance the efficacy of targeted therapy for HCC through combination strategies. Combination treatments involving targeted therapy for advanced HCC are compared and discussed.

| S-EPMC5342607 | biostudies-literature

Immunotherapy in Advanced Prostate Cancer-Light at the End of the Tunnel?

Project description:Immunotherapeutic treatment approaches are now an integral part of the treatment of many solid tumors. However, attempts to integrate immunotherapy into the treatment of prostate cancer have been disappointing so far. This is due to a highly immunosuppressive, "cold" tumor microenvironment, which is characterized, for example, by the absence of cytotoxic T cells, an increased number of myeloid-derived suppressor cells or regulatory T cells, a decreased number of tumor antigens, or a defect in antigen presentation. The consequence is a reduced efficacy of many established immunotherapeutic treatments such as checkpoint inhibitors. However, a growing understanding of the underlying mechanisms of tumor-immune system interactions raises hopes that immunotherapeutic strategies can be optimized in the future. The aim of this review is to provide an overview of the current status and future directions of immunotherapy development in prostate cancer. Background information on immune response and tumor microenvironment will help to better understand current therapeutic strategies under preclinical and clinical development.

| S-EPMC8910587 | biostudies-literature

Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy.

Project description:Advanced hepatocellular carcinoma (HCC) is a severe malignancy that poses a serious threat to human health. Owing to challenges in early diagnosis, most patients lose the opportunity for radical treatment when diagnosed. Nonetheless, recent advancements in cancer immunotherapy provide new directions for the treatment of HCC. For instance, monoclonal antibodies against immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC. However, tumor cells can evade the immune system through various mechanisms. With the rapid development of genetic engineering and molecular biology, various new immunotherapies have been used to treat HCC, including ICIs, chimeric antigen receptor T cells, engineered cytokines, and certain cancer vaccines. This review summarizes the current status, research progress, and future directions of different immunotherapy strategies in the treatment of HCC.

| S-EPMC10900147 | biostudies-literature

Therapy in Advanced Hepatocellular Carcinoma.

Project description:Treatment of advanced hepatocellular carcinoma (HCC) is challenging. Several randomized clinical trials are investigating the efficacy of systemic therapy, immunotherapy, and locoregional therapy as monotherapy or combined with other modalities in the treatment of HCC. Systemic therapy is the preferred treatment in advanced disease. To date, multiple first-line and second-line agents received Food and Drug Administration approval. For over a decade, sorafenib was the only first-line agent. In May 2020, combination of atezolizumab and bevacizumab has been approved as a first-line systemic regimen. Lenvatinib is another first-line agent that has multikinase activity. Second-line agents include cabozantinib, regorafenib, ramucirumab, and nivolumab. Adoptive cell transfer therapy is a highly specific immunotherapy that has shown antitumor activity against HCC. Oncolytic viruses are genetically modified viruses that infect cancer cells and induce apoptosis. Locoregional therapies such as transarterial chemoembolization and radioembolization have shown a potential benefit in selected patients with advanced HCC. In this review, we aim to summarize the treatment options available for advanced HCC.

| S-EPMC7732574 | biostudies-literature

Combination therapies for advanced hepatocellular carcinoma: a beacon of light or a castle in the air.

Project description: Not available

| S-EPMC9396096 | biostudies-literature

Immune-Based Combination Therapies for Advanced Hepatocellular Carcinoma.

Project description:Hepatocellular carcinoma (HCC) is the fourth most frequent cause of cancer-related death worldwide. HCC frequently presents as advanced disease at diagnosis, and disease relapse following radical surgery is frequent. In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC, particularly with the introduction of atezolizumab/bevacizumab as the new standard of care for first-line treatment. Recently, dual immune checkpoint blockade with durvalumab plus tremelimumab has also emerged as an effective first-line treatment for advanced HCC and most of the research is currently focused on developing combination treatments based mainly on ICIs. In this review, we will discuss the rationale and ongoing clinical trials of immune-based combination therapies for the treatment of advanced HCC, also focusing on new immunotherapy strategies such as chimeric antigen receptor T cells (CAR-T) and anti-cancer vaccines.

| S-EPMC10493094 | biostudies-literature

Bispecific antibodies for cancer therapy: the light at the end of the tunnel?

Project description:With 23 approvals in the US and other countries and four approvals outside US, antibodies are now widely recognized as therapeutic molecules. The therapeutic and commercial successes met by rituximab, trastuzumab, cetuximab and other mAbs have inspired antibody engineers to improve the efficacy of these molecules. Consequently, a new wave of antibodies with engineered Fc leading to much higher effector functions such as antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity is being evaluated in the clinic, and several approvals are expected soon. In addition, research on a different class of antibody therapeutics, bispecific antibodies, has recently led to outstanding clinical results, and the first approval of the bispecific antibody catumaxomab, a T cell retargeting agent that was approved in the European Union in April 2009. This review describes the most recent advances and clinical study results in the field of bispecific antibodies, a new class of molecules that might outshine conventional mAbs as cancer immunotherapeutics in a near future.

| S-EPMC2791310 | biostudies-literature

Systemic therapy in advanced hepatocellular carcinoma.

Project description: Not available

| S-EPMC10121316 | biostudies-literature

Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma.

Project description:PurposeTo determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) and veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC).MethodsThis single-arm phase II trial enrolled patients with pathologically confirmed, sorafenib-refractory HCC. All patients received 40 mg ABT-888 PO daily on days 1-7 and 150 mg/m(2) TMZ PO daily on days 1-5 of a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. Tumor response was assessed every 2 cycles using RECIST criteria, and toxicities were assessed using CTCAE v4.03.ResultsWe enrolled 16 patients in the first phase of the trial, but the study was discontinued due to a poor ORR; only four patients (25 %) had SD after 2 cycles. Twelve patients (75 %) were taken off study after 2 months of treatment; 10 of these had disease progression. Two patients (13 %) were taken off study due to severe toxicity, and one patient (6 %) died from non-treatment-related liver failure. One patient had SD for 16 months, receiving 11 cycles of therapy before being taken off study. The most common grade 3 treatment-related toxicities included vomiting (n = 2), thrombocytopenia (n = 2), nausea (n = 1), and anemia (n = 1). The median PFS was 1.9 months, and median OS was 13.1 months.ConclusionThe combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC. However, the regimen failed to show survival benefit. CLINICALTRIALS.Gov identifierNCT01205828.

| S-EPMC4612326 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data