scholarly journals Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Gaetano Bertino ◽  
Shirin Demma ◽  
Annalisa Ardiri ◽  
Maria Proiti ◽  
Giulia Malaguarnera ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Web Of Science ◽  
Malignant Tumors ◽  
Tumor Staging ◽  
Treatment Options ◽  
Advanced Hcc ◽  
The Past ◽  
Dismal Prognosis ◽  
Keywords Hepatocellular Carcinoma

Background. Hepatocellular carcinoma is one of the most common and lethal malignant tumors worldwide. Over the past 15 years, the incidence of HCC has more than doubled. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with HCC. A better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy. Materials and Methods. A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” and “immunotherapy.” Discussion and Conclusion. Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension, and the underlying degree of liver dysfunction. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.

scholarly journals Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 526 ◽  
Author(s):  
Alqahtani ◽  
Khan ◽  
Alloghbi ◽  
Said Ahmed ◽  
Ashraf ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Advanced Hcc ◽  
Complex Process ◽  
Clinical Benefits ◽  
Approved Drugs

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors worldwide. HCC is a complex process that is associated with several etiological factors, which in turn result in aberrant activation of different cellular and molecular pathways and the disruption of balance between activation and inactivation of protooncogenes and tumor suppressor genes, respectively. Since HCC most often occurs in the setting of a diseased or cirrhotic liver and most of the patients are diagnosed at the late stage of disease, prognosis is generally poor. At present, limited treatment options with marginal clinical benefits are available. Systemic therapy, particularly in the form of conventional cytotoxic drugs, are generally ineffective. In recent years, molecular-targeted therapies have been clinically used to treat various cancers, including liver cancer. This approach inhibits the growth of tumor cells by interfering with molecules that are involved in carcinogenesis, which makes it more selective and specific than cytotoxic chemotherapy. Many clinical trials have been carried out while using molecular targeted drugs in advanced HCC with many more in progress. The clinical trials in HCC to date have evaluated a single-targeted therapy alone, or two or more targeted therapies in parallel. The aim of this review is to provide insight of various molecular mechanisms, leading to HCC development and progression, and also the range of experimental therapeutics for patients with advanced HCC. The review will summarize different clinical trials data the successes and failures of these treatments, as well as the most effective and approved drugs designed against HCC.

scholarly journals Recent advances in systemic therapy for hepatocellular carcinoma

2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Huajun Zhang ◽  
Wuyang Zhang ◽  
Longying Jiang ◽  
Yongheng Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Targeted Therapy ◽  
Systemic Treatment ◽  
Malignant Tumors ◽  
Targeted Agents ◽  
Rapid Progress ◽  
Advanced Hcc ◽  
The Past ◽  
The World ◽  
Systemic Drug

AbstractHepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors in the world. Therapeutic options for advanced HCC are limited. Systemic treatment, especially with conventional cytotoxic drugs, is usually ineffective. For more than a decade, sorafenib has been the only systemic drug that has been proven to be clinically effective for treating advanced HCC. However, over the past three years, the rapid progress of molecular targeted therapies has dramatically changed the treatment landscape for advanced HCC. Immune checkpoint therapies are now being incorporated into HCC therapies, and their combination with molecular targeted therapy is emerging as a tool to enhance the immune response. In this review, we summarize the development and progress of molecular targeted agents and immunotherapies in HCC.

scholarly journals Viral hepatitis associated hepatocellular carcinoma on the African continent, the past, present, and future: a systematic review

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ottovon Bismark Dakurah ◽  
Cynthia Raissa Tchuem Tamandjou ◽  
Moleen Zunza ◽  
Wolfgang Preiser ◽  
Tongai Gibson Maponga
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Hepatitis B ◽  
Viral Hepatitis ◽  
Web Of Science ◽  
African Continent ◽  
Inclusion Criteria ◽  
Hepatitis D ◽  
The Past ◽  
B Virus

Abstract Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in Africa. In Africa, the major causes of HCC include chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Knowledge of the changes in the incidence of viral hepatitis-associated HCC over time and the factors responsible for such changes is key in informing policies for the prevention of viral hepatitis-associated HCC in Africa. Aim The study aimed to systematically summarize the changes in the prevalence of viral hepatitis among HCC patients and the overall effect of the prevalence of viral hepatitis on the incidence of HCC over the past four decades in Africa (1980–2019). Methods A literature search was conducted in MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Web of Science, and African wide web for articles published on viral hepatitis-associated HCC in Africa from 1980 to 2019. The abstracts of the articles were screened for eligibility and those meeting the inclusion criteria were retrieved and reviewed. Results A total of 272 studies were included in the analysis. Viral hepatitis-related HCC incidence changed by 1.17% (95% confidence interval (CI): 0.63–1.71, p < 0.001), 0.82% (95% CI: 0.45–1.18, p < 0.001), and 3.34% (95% CI: 2.44–4.25, p < 0.001) for every 1% change in the prevalence of HBV, HCV, and hepatitis D virus (HDV) respectively, per decade. The incidence of HBV-related HCC decreased by − 0.50% (95% CI: − 0.74 – − 0.25, p < 0.001) over the last 40 years, while HCV-related HCC increased. Conclusion Overall, the incidence of viral hepatitis-associated HCC has not declined, mainly due to no decline in the prevalence of HCV, HDV, and the high number of chronic hepatitis B carriers on the African continent. There is an urgent need for the allocation of resources for the implementation of treatment and preventive programs for HBV, HCV, HDV, and HCC in Africa. This systematic review is registered with PROSPERO®, number CRD42020169723.

A Review of the Management of Hepatocellular Carcinoma: Standard Therapy and a Look to New Targets

2012 ◽  
pp. 275-280
Author(s):  
Andrew X. Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Options ◽  
Mechanisms Of Action ◽  
Targeted Agents ◽  
Adjuvant Setting ◽  
Advanced Hcc ◽  
Molecularly Targeted Agents ◽  
Drug Eluting Beads ◽  
Drug Eluting ◽  
New Treatment

Overview: Management of hepatocellular carcinoma (HCC) continues to be challenging, but new treatment options are evolving. A multidisciplinary evaluation will help make the best treatment decisions for each patient. Although we continue to improve the outcomes of curative treatment with resection, liver transplant, and radiofrequency ablation (RFA), many new liver-directed regional therapies including drug-eluting beads, radioembolization, and radiation are emerging. Sorafenib remains the only approved agent for advanced HCC, and its role in the adjuvant setting following resection or RFA, with transarterial chemoembolization, or in combination with other targeted agents or chemotherapy in the advanced stage is under investigation. Many molecularly targeted agents with novel mechanisms of action are under active development.

Plasma Osteopontin Level as a Diagnostic Marker of Hepatocellular Carcinoma in Patients with Radiological Evidence of Focal Hepatic Lesions

2013 ◽  
Vol 99 (1) ◽  
pp. 100-107 ◽  
Author(s):  
Ashraf Khalil ◽  
Jamalat Elgedawy ◽  
Mohammed F Faramawi ◽  
Ashraf Elfert ◽  
Ibrahim Salama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Alpha Fetoprotein ◽  
Egyptian Patients ◽  
Diagnostic Role ◽  
Focal Hepatic Lesions ◽  
Serum Alpha Fetoprotein ◽  
Hepatic Lesions

Aims Hepatocellular carcinoma is one of the most aggressive malignant tumors and has limited treatment options. Needle-guided biopsies have been utilized as a tool to diagnose malignant focal hepatic lesions. These techniques are discouraged because of their complications. Nowadays, alpha fetoprotein is the most widely used tumor marker for screening and diagnosis of hepatocellular carcinoma. Nevertheless, this marker has limitations. The diagnostic role of plasma osteopontin as an adjuvant or alternative marker to alpha fetoprotein to detect hepatocellular carcinoma in Egyptian patients with focal hepatic lesions was evaluated in this study. Subject and methods Eighty participants were recruited from the Egyptian National Liver Institute and were self-assigned to three groups, namely, focal hepatic lesions (n = 40), liver cirrhosis (n = 20), and controls (n = 20). Participants' plasma osteopontin and serum alpha fetoprotein levels were determined and were compared across the three groups. Results The discriminatory ability of plasma osteopontin for hepatocellular carcinoma was lower than that of alpha fetoprotein. Osteopontin and alpha fetoprotein were not correlated with each other. Neither the gender nor the age of the patients showed a significant association with plasma osteopontin level. Conclusion Measuring plasma osteopontin level alone has no advantage over serum alpha fetoprotein in patients with focal hepatic lesions due to chronic liver disease.

RADIOTHERAPY AND TARGETED THERAPY IN PATIENTS WITH METASTATIC BRAIN LESION: NEW TREATMENT OPTIONS

2017 ◽  
Vol 63 (5) ◽  
pp. 684-694
Author(s):  
Sergey Banov ◽  
Andrey Golanov ◽  
Yelena Vetlova ◽  
Aleksandr Redkin
Keyword(s):  
Targeted Therapy ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Brain Lesion ◽  
Local Treatment ◽  
Treatment Technique ◽  
Clinical Implementation ◽  
Whole Brain Irradiation ◽  
The Creation ◽  
The Brain

Metastases in the brain are the most common malignant brain tumor. A multidisciplinary approach including radiotherapy, surgery and chemotherapy is used to treat patients with brain metastases depending on the prevalence of the tumor process and symptomatology. In recent years there was a steady trend of transition from conventional to conformal radiotherapy. A confirmation of this fact is the creation and clinical implementation of the principles of stereotactic radiotherapy (in the mode of radiosurgery or hypofractionation), which in fact changed the paradigm of local treatment of patients with metastases in the brain. On the other hand the evolution of drug treatment of malignant tumors led to the creation of a new direction - targeted therapy, which significantly changed the treatment of cancer patients. The combination of radiotherapy and targeted therapy contributed to further individualization of treatment, potentially eliminating the need for cytotoxic chemotherapy or whole brain irradiation. At present the effectiveness and safety of the combination of radiotherapy and targeted therapy are being studied, the results of which will determine the place and role of the treatment technique in treatment of patients with metastatic brain lesion. This review summarizes the available literature data of a combination of radiotherapy and targeted therapy in patients with metastatic brain lesion with an emphasis on survival, local control, distant metastasis and post-radiation complications.

Surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: Meta-analysis of randomized controlled trials.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 454-454
Author(s):  
Kyung-Hun Lee ◽  
Dae-Won Lee ◽  
Myoung-Jin Jang ◽  
Tae-Yong Kim ◽  
Sae-Won Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Molecular Targeted Therapy ◽  
Treatment Effects ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Incremental Benefit ◽  
Randomized Controlled

454 Background: Time to progression (TTP) is suggested as a reliable endpoint compared to progression free survival (PFS) in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied. Methods: We searched Pubmed and Embase data to obtain data source. Eligible studies were randomized controlled phase III trials which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association of treatment effects as shown by the hazard ratio (HR) of TTP and OS in each trial was assessed by Spearman rank correlation coefficient ( rs) and linear regression analysis. The association between median TTP and OS was also investigated. Results: Nine studies with a total of 18 treatment arms and 6318 patients were included. Incremental benefit from the study treatment in TTP from each trial was correlated with incremental benefit in OS. The rs value and R2 value between log (HRTTP) and log (HROS) was 0.73 (95% CI 0.12 – 0.94, p = 0.024) and 0.57. The minimum TTP effect to predict a treatment effect on OS was 0.63. Median TTP was associated with median OS. The rs value between TTP and OS was 0.73 (95% confidence interval (CI) 0.40 – 0.89, p < 0.001) and the corresponding R2 was 0.42. Conclusions: Our study results suggest that TTP could be used as a surrogate marker for OS in the clinical trials of advanced HCC. However, the results suggest modest correlation between treatment effects on TTP and OS. Along with individual-level analysis more evidences are needed to confirm our finding.

scholarly journals Role of Multidisciplinary Care in the Management of Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Kia Byrd ◽  
Saleh Alqahtani ◽  
Adam C. Yopp ◽  
Amit G. Singal
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multidisciplinary Approach ◽  
Treatment Options ◽  
Multidisciplinary Care ◽  
Multimodal Approach ◽  
Poor Survival ◽  
The Past ◽  
Different Types ◽  
Potential Structure

AbstractDespite advances in treatment options for hepatocellular carcinoma (HCC), 5-year survival for HCC remains below 20%. This poor survival is multifactorial but is partly related to underuse of curative treatment in clinical practice. In light of growing treatment options, delivered by different types of providers, optimal management requires input from multiple specialties. A multidisciplinary approach has been evolving over the past couple of decades, bringing different specialists together to develop a therapeutic plan to treat and manage HCC, which significantly increases timely guideline-concordant treatment and improves overall survival. The present review attempts to highlight the need for such a multimodal approach by providing insights on its potential structure and impact on the various aspects of HCC management.

scholarly journals Intrahepatic Cholangiocarcinoma: State of the Art of FGFR Inhibitors

2021 ◽  
Vol 28 ◽  
pp. 107327482198931
Author(s):  
Tianyu Wu ◽  
Xiaoqing Jiang ◽  
Xin Zhang ◽  
Bodeng Wu ◽  
Bin Xu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Intrahepatic Cholangiocarcinoma ◽  
Web Of Science ◽  
State Of The Art ◽  
Early Stage ◽  
Comprehensive Treatment ◽  
Primary Liver Tumor ◽  
The Past ◽  
Treatment Measures

Objective: Intrahepatic cholangiocarcinoma (iCCA), the second most common type of primary liver tumor, has an increasing incidence in the past few decades. iCCA is highly malignant, with a 5-year survival rate of approximately 5-10%. Surgical resection is usually the prescribed treatment for patients with early stage iCCA; however, patients are usually in an advanced stage iCCA upon diagnosis. Currently, targeted therapy combined with chemotherapy and other comprehensive treatment measures have been mainly adopted as palliative treatment measures. As a common candidate of targeted therapy, FGFR inhibitors have demonstrated their unique advantages in clinical trials. At present, the prospect of FGFR targeted therapy is encouraging. The landscape of FGFR inhibitors in iCCA is needed to be showed urgently. Methods: We searched relative reports of clinical trials on FGFR inhibitors in PubMed as well as Web of Science. We also concluded other available clinical trials of FGFR inhibitors (Data were collected from clinicaltrials.gov ). Results: Several relatively effective targeted drugs are being used in clinical trials. Some preliminary results indicate the outlook of targeted therapy such as BGJ398, TAS120, and HSP90 inhibitors. Conclusions: In summary, FGFR targeted therapy has broad prospects for the treatment of iCCA.

scholarly journals Trends in treatment for hepatocellular carcinoma in Japan

2021 ◽  
Vol 9 (7) ◽  
Author(s):  
Yoshihiro Sakamoto ◽  
Ryota Matsuki ◽  
Takaaki Arai ◽  
Masaharu Kogure ◽  
Yutaka Suzuki
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vascular Invasion ◽  
Treatment Options ◽  
Multidisciplinary Treatment ◽  
Antiviral Agents ◽  
Quarter Century ◽  
Alcoholic Fatty Liver ◽  
Advanced Hcc ◽  
Extrahepatic Metastases ◽  
Japanese Guideline

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer deaths in Japan, and it has gradually decreased in the last quarter century. The reason for the decrease in HCC patients is the decrease of patients with hepatitis C virus due to avoiding unnecessary blood transfusions and development of direct-acting antiviral agents (DAAs), which have been available since 2014, along with interferon and oral antiviral agents in Japan. On the other hand, the numbers of HCC patients with non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) are increasing. In the treatment strategy for HCC in the Japanese guideline, the algorithm involves five clinicopathological factors: liver function (assessed using the Child-Pugh classification, liver damage score, and the ICG-R15 value), presence of extrahepatic metastases, presence of vascular invasion, number of tumors (within 3 or more than 4), and tumor size (within 3 cm or over 3 cm). Surgical resection is sometimes indicated for extrahepatic metastases in patients with well-controlled intrahepatic HCC, and for advanced HCC with vascular invasion, hepatectomy is also recommended as one of the treatment options according to the results of a nationwide survey in Japan. In the latest Japanese guideline, the recommended chemotherapy for advanced HCC is lenvatinib or sorafenib as first-line and regorafenib as second-line therapy. Currently, based on the results of various clinical trials for advanced HCC, the therapeutic options for advanced HCC have increased, such as combination therapy of atezolizumab and bevacizumab, ramucirumab, and cabozantinib. Reports of conversion surgery after chemotherapy have also increased, and the development of multidisciplinary treatment for advanced HCC will be of further interest in the future.

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