Frontiers in Anti-Cancer Drug Discovery

Volume: 4

Molecular Targeted Drugs under Investigation in Hepatocellular Carcinoma

Author(s): Mohamed Bouattour and Johanna Wassermann

Pp: 39-87 (49)

DOI: 10.2174/978160859225114040004

* (Excluding Mailing and Handling)

Abstract

Until no far past, advanced hepatocellular carcinoma (HCC) was considered as an “orphan” disease in terms of effective molecules when compared with other highly prevalent cancers worldwide. Recently, HCC -a tumor renowned to be refractory to systemic chemotherapy- has attracted wide interest as a result of improved understanding of its molecular biology and pathogenesis. HCC is a well-vascularized tumor in which angiogenesis is strongly implicated for aggressiveness and dissemination and targeted drugs (mainly angiogenesis inhibitors) have been tested to block neovessels and various signaling pathways involved in this disease. This approach has been successful, at least for sorafenib -an antiangiogenic and multikinase inhibitoracross 2 large international randomized phase III trials confirming the efficacy and safety of this compound as validated option in patients with advanced-stage HCC.

Approval of sorafenib as the new standard care for advanced HCC raised the interest to investigate plethora of drugs in this pathology and in different setting including earlier stages, and as adjuvant therapy. Currently, several small molecules and antiangiogenic agents are investigated in preclinical and clinical studies with disparate outcomes, with the hope to identify new efficient therapies, thereby opening new prospects but also raising several unmet needs.

This review develops the rational for using these emerging drugs in treatment algorithm of HCC, and highlights the strength and limits of novel compounds with focus on specific challenges for their clinical development.


Keywords: Angiogenesis inhibitors, brivanib, combination therapy, hepatocellular carcinoma, MET inhibitors, mTOR inhibitors, new compounds, regorafenib, sorafenib, sunitinib.

Related Journals
Related Books
© 2024 Bentham Science Publishers | Privacy Policy