scholarly journals Modulation of the Autophagy-Lysosomal Pathway in Hepatocellular Carcinoma Using Small Molecules

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1580 ◽  
Author(s):  
Yu Geon Lee ◽  
Tae–Il Jeon
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Molecules ◽  
Treatment Strategy ◽  
Energy Homeostasis ◽  
Systemic Treatment ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Degradation Pathway ◽  
Early Stage Disease ◽  
Stage Disease

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all cases of primary liver cancer; it is the third most frequent cause of cancer-related death worldwide. In early-stage disease, surgical resection and liver transplantation are considered curative treatments. However, the majority of HCC patients present with advanced-stage disease that is treated using palliative systemic therapy. Since HCC is heterogeneous owing to its multiple etiologies, various risk factors, and inherent resistance to chemotherapy, the development of an effective systemic treatment strategy for HCC remains a considerable challenge. Autophagy is a lysosome-dependent catabolic degradation pathway that is essential for maintaining cellular energy homeostasis. Autophagy dysfunction is closely linked with the pathogenesis of various cancers; therefore, the discovery of small molecules that can modulate autophagy has attracted considerable interest in the development of a systemic treatment strategy for advanced HCC. Here, we reviewed the roles of autophagy in HCC and the recent advances regarding small molecules that target autophagy regulatory mechanisms.

New advances in the diagnosis and management of hepatocellular carcinoma

BMJ ◽  
2020 ◽  
pp. m3544 ◽  
Author(s):  
Ju Dong Yang ◽  
Julie K Heimbach
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Treatment ◽  
Early Stage ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Long Term Outcomes ◽  
Stage Disease

ABSTRACT Hepatocellular carcinoma is one of the leading causes of cancer related death in the world. Biannual surveillance for the disease in patients with cirrhosis and in high risk carriers of hepatitis B virus allows early stage cancer detection and treatment with good long term outcomes. Liver ultrasonography and serum α fetoprotein are the most commonly used surveillance tests. If suspicious results are found on the surveillance test, multiphasic computed tomography or magnetic resonance imaging should be undertaken to confirm the diagnosis of hepatocellular carcinoma. If radiologic tests show inconclusive results, liver biopsy or repeat imaging could be considered for confirmation of hepatocellular carcinoma. Management of the disease is complex. Patients should be evaluated by a multidisciplinary team, and the selection of treatment should consider factors such as tumor burden, severity of liver dysfunction, medical comorbidities, local expertise, and preference of patients. Early stage hepatocellular carcinoma is best managed by curative treatment, which includes resection, ablation, or transplantation. Patients with intermediate stage disease often receive locoregional treatment. Systemic treatment is reserved for patients with advanced disease. Several positive, phase III, randomized controlled trials have expanded the systemic treatment options for advanced hepatocellular carcinoma with promising long term outcomes, especially trials using combination treatments, which could also have eventual implications for the treatment of earlier stage disease.

Role of MicroRNA in the Diagnosis and Management of Hepatocellular Carcinoma

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 25-40 ◽  
Author(s):  
Ioannis A. Ziogas ◽  
Georgios Sioutas ◽  
Konstantinos S. Mylonas ◽  
Georgios Tsoulfas
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Tumors ◽  
Early Stage ◽  
Survival Rates ◽  
Chemotherapeutic Agents ◽  
Diagnostic Methods ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Underlying Mechanisms

Introduction: Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world and comes third in cancer-induced mortality. The need for improved and more specific diagnostic methods that can detect early-stage disease is immense, as it is amenable to curative modalities, while advanced HCC is associated with low survival rates. microRNA (miRNA) expression is deregulated in HCC and this can be implemented both diagnostically and therapeutically. Objective: To provide a concise review on the role of miRNA in diagnosis, prognosis, and treatment of HCC. Method: We conducted a comprehensive review of the PubMed bibliographic database. Results: Multiple miRNAs are involved in the pathogenesis of HCC. Measurement of the levels of these miRNAs either in tumor tissue or in the blood constitutes a promising diagnostic, as well as prognostic tool. OncomiRs are miRNAs that promote tumorigenesis, thus inhibiting them by administering antagomiRs is a promising treatment option. Moreover, replacement of the depleted miRNAs is another potential therapeutic approach for HCC. Modification of miRNA levels may also regulate sensitivity to chemotherapeutic agents. Conclusion: miRNA play a pivotal role in HCC pathogenesis and once the underlying mechanisms are elucidated, they will become part of everyday clinical practice against HCC.

scholarly journals Current frontline approaches in the management of hepatocellular carcinoma: the evolving role of immunotherapy

2018 ◽  
Vol 11 ◽  
pp. 175628481880808 ◽  
Author(s):  
Gagandeep Brar ◽  
Tim F. Greten ◽  
Zachary J. Brown
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Rate ◽  
Early Stage ◽  
Standard Of Care ◽  
Good Prognosis ◽  
Current Standard ◽  
Early Stage Disease ◽  
Advanced Hcc ◽  
Stage Disease

Hepatocellular carcinoma (HCC) is a major cause of cancer-associated mortality worldwide and is expected to rise. Patients with early-stage disease may have a good prognosis with a 5-year survival rate of greater than 70%. However, the majority of patients are diagnosed with late-stage disease with a dismal overall survival rate of less than 16%. Therefore, there is a great need for advances in the treatment of advanced HCC, which for approximately the past decade, has been sorafenib. Immunotherapy is an evolving cancer treatment and has shown promise in treating patients with advanced HCC. In this review, we discuss the current standard of care for advanced HCC and then discuss the evolving role of immunotherapies.

scholarly journals New Frontiers in the Medical Therapy of Hepatocellular Carcinoma

Chemotherapy ◽  
2022 ◽  
Author(s):  
Claudia Angela Maria Fulgenzi ◽  
Antonio D'Alessio ◽  
Thomas Talbot ◽  
Alessandra Gennari ◽  
Mark R. Openshaw ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Phase Iii ◽  
Early Stage Disease ◽  
Primary Liver Tumor ◽  
Phase Iii Clinical Trials ◽  
Stage Disease ◽  
Major Treatment

Background: Hepatocellular carcinoma (HCC) is the most common primary liver tumor, and it rates fourth as a cause of cancer-related death. The presence of underlying liver disease and poor chemosensitivity pose major treatment challenges in the management of HCC. However, in the last few years the therapeutic scenario has substantially changed, and immunotherapy in the form of immune checkpoint inhibitors (ICPIs) has become an essential therapeutic strategy in this field. Summary: After controversial results of monotherapy, ICPIs have been mainly investigated in association with anti-angiogenic agents or as dual checkpoint inhibition. The combination of atezolizumab plus bevacizumab has become the new therapeutic standard for unresectable HCC. Currently, a number of ICPIs-based combinations are being studied in phase III clinical trials as front-line therapy for advanced HCC, with growing interest in integration of early-stage disease management in the form of adjuvant or neoadjuvant therapies. With most of the trials investigating ICPIs as first line treatment, the second line scenario relies mainly on tyrosine kinase inhibitors, which however, have not been formally trialed after ICPIs. Key messages: In this review we summarize the main therapeutic advances in the systemic management of HCC focusing on the most relevant ongoing trials. We also discuss the main issues arising from a such rapidly evolving field including therapeutic sequencing and patient stratification.

Hepatic, neuroendocrine, and general oncological emergencies

2013 ◽  
pp. 329-341
Author(s):  
Daniel Marks ◽  
Marcus Harbord
Keyword(s):  
Hepatocellular Carcinoma ◽  
Viral Infection ◽  
Neuroendocrine Tumours ◽  
Early Stage ◽  
Hepatic Malignancy ◽  
Early Stage Disease ◽  
Emergency Presentation ◽  
Common Cancer ◽  
Stage Disease

Emergency presentation of hepatic malignancy Emergency presentations of neuroendocrine tumours General oncological emergencies Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. It usually develops on the background of cirrhosis, most frequently as a result of chronic hepatotropic viral infection. Untreated, the majority of patients die within 1y of diagnosis. However, there are now a number of potentially curative options for patients diagnosed with early stage disease, and overall 5y survival is between 50–70% in specialist centres....

scholarly journals Atezolizumab and bevacizumab for hepatocellular carcinoma: mechanism, pharmacokinetics and future treatment strategies

2021 ◽  
Author(s):  
Xiufeng Liu ◽  
Yi Lu ◽  
Shukui Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint Inhibitor ◽  
Early Stage ◽  
Treatment Strategies ◽  
Future Directions ◽  
Early Stage Disease ◽  
Combination Strategies ◽  
Common Cancer ◽  
Stage Disease ◽  
Inhibitor Combination

Hepatocellular carcinoma (HCC) is a common cancer globally and a leading cause of cancer-related deaths. Although early-stage disease may be curable by resection, liver transplantation or ablation, many patients present with unresectable disease and have a poor prognosis. Combination treatment with atezolizumab (targeting PD-L1) and bevacizumab (targeting VEGF) in the recent IMbrave150 study was shown to be effective with an acceptable safety profile in patients with unresectable HCC. Herein, we discuss this novel combination in the context of the liver immune environment, summarize the mechanism and pharmacokinetics of atezolizumab and bevacizumab, and examine recent data on other immune checkpoint inhibitor combination strategies as well as future directions in the treatment of patients with advanced HCC.

Understanding variations in referral patterns and treatment choices for patients with hepatocellular carcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 293-293
Author(s):  
Omar Hyder ◽  
David Cosgrove ◽  
Hari Nathan ◽  
Kenzo Hirose ◽  
Christopher Lee Wolfgang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Interventional Radiology ◽  
Medical Oncology ◽  
Early Stage ◽  
Geographic Location ◽  
Subsequent Treatment ◽  
Early Stage Disease ◽  
Factors Associated ◽  
Stage Disease ◽  
Younger Age

293 Background: Patterns of care of physician specialists may differ for patients with hepatocellular carcinoma(HCC). The extent and reasons underlying possible variations are poorly understood. One source of variation may be disparate referral rates to specialists leading to differences in cancer-directed treatments. Methods: We queried the Surveillance, Epidemiology, and End Results(SEER) linked Medicare database for patients with HCC diagnosed between 1998-2007 who consulted one or more physicians following diagnosis. Visit and procedure records were abstracted from Medicare billing records and factors associated with visiting a specialist and subsequent treatment were examined. Results: 6752 patients with HCC were identified;median age was 73 yrs and the majority was male(66%), White(60%) and from a West geographical region(56%). 1379(20%) patients had early-stage disease. In the six months after diagnosis, referral to a specialist varied considerably (hepatology/gastroenterology-60%; medical oncology-62%; surgery-56%; interventional radiology-33%; radiation oncology-9%). 22% patients saw one specialist, while 39% saw ≥3 specialists. Time between diagnosis and visitation with a specialist varied by sub-specialty (surgery-37 days vs. interventional radiology-55 days;P=0.04). Factors associated with referral to a specialist included younger age(OR=2.13), geographic location(Northeast OR=2.09), and presence of early-stage disease(OR=2.21)(all P<0.05). Among patients with early-stage disease, 77% saw a surgeon, while 50% had a medical oncology consultation. Receipt of therapy among patients with early-stage disease varied (no therapy-30%; surgery-39%; interventional radiology-9%; other-22%). Factors associated with receipt of therapy included younger age(OR=2.82), as well as time to consultation with cancer specialist(OR=1.05)(both P<0.05). Conclusions: Following HCC diagnosis, referral to a specialist varied considerably. Both clinical and non-clinical factors were associated with consultation. Variations in referral to a specialist and subsequent therapy need to be better understood to ensure all HCC patients receive appropriate care.

Novel approaches to improve prostate cancer diagnosis and management in early-stage disease

2012 ◽  
Vol 109 ◽  
pp. 1-7 ◽  
Author(s):  
Michael Marberger ◽  
Jelle Barentsz ◽  
Mark Emberton ◽  
Jonas Hugosson ◽  
Stacy Loeb ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Diagnosis ◽  
Early Stage ◽  
Early Stage Disease ◽  
Prostate Cancer Diagnosis ◽  
Diagnosis And Management ◽  
Stage Disease ◽  
Novel Approaches ◽  
Improve Prostate Cancer

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

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