We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Insights in Molecular Therapies for Hepatocellular Carcinoma.
- Authors
Heumann, Philipp; Albert, Andreas; Gülow, Karsten; Tümen, Deniz; Müller, Martina; Kandulski, Arne
- Abstract
Simple Summary: Molecular directed therapy for hepatocellular carcinoma (HCC) involves targeting specific signaling pathways that normally promote cancer cell growth and survival. Accordingly, a blockage of these pathways leads to tumor shrinkage and improves the patient outcome. Recent advancements in molecular directed therapies have focused on tyrosine kinase and angiogenesis inhibition, thus targeting pathways involved in the molecular pathogenesis of HCC. Especially the vascular endothelial growth factor (VEGF) signaling pathway is one of the most prominent pathways involved in HCC progression. The combination of inhibiting VEGF signaling and immune-directed therapy or double immunocheckpoint inhibition are the mainstay of contemporary treatment strategies and promising agents for future combination treatment regimens. However, the effectiveness of these therapies may vary among patients, highlighting the need to identify the specific molecular alterations for tailored therapeutic approaches. Additionally, in modern systemic therapy of patients with HCC, the underlying pathology of the liver has always been encountered to identify population subgroups in terms of pathophysiology and underlying liver function to predict response to different therapeutic regimens. We conducted a comprehensive review of the current literature of published data and clinical trials (MEDLINE), as well as published congress contributions and active recruiting clinical trials on targeted therapies in hepatocellular carcinoma. Combinations of different agents and medical therapy along with radiological interventions were analyzed for the setting of advanced HCC. Those settings were also analyzed in combination with adjuvant situations after resection or radiological treatments. We summarized the current knowledge for each therapeutic setting and combination that currently is or has been under clinical evaluation. We further discuss the results in the background of current treatment guidelines. In addition, we review the pathophysiological mechanisms and pathways for each of these investigated targets and drugs to further elucidate the molecular background and underlying mechanisms of action. Established and recommended targeted treatment options that already exist for patients are considered for systemic treatment: atezolizumab/bevacizumab, durvalumab/tremelimumab, sorafenib, lenvatinib, cabozantinib, regorafenib, and ramucirumab. Combination treatment for systemic treatment and local ablative treatment or transarterial chemoembolization and adjuvant and neoadjuvant treatment strategies are under clinical investigation.
- Subjects
THERAPEUTIC use of antineoplastic agents; VASCULAR endothelial growth factors; ANTINEOPLASTIC agents; PROTEIN-tyrosine kinase inhibitors; IMMUNOTHERAPY; CELLULAR signal transduction; NEOVASCULARIZATION inhibitors; CELL lines; IMMUNE checkpoint inhibitors; CELL survival; HEPATOCELLULAR carcinoma; MOLECULAR pathology; DISEASE progression; PHARMACODYNAMICS
- Publication
Cancers, 2024, Vol 16, Issue 10, p1831
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16101831