Molecular Targeted Drugs under Investigation in Hepatocellular Carcinoma
Pp. 39-87 (49)
Mohamed Bouattour and Johanna Wassermann
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.
Angiogenesis inhibitors, brivanib, combination therapy,
hepatocellular carcinoma, MET inhibitors, mTOR inhibitors, new compounds,
regorafenib, sorafenib, sunitinib.
Department of Hepatology, Beaujon University Hospital, Assistance Publique-Hôpitaux de Paris, 100 BLD Général Leclerc 92118 Clichy, France.