Researchers of the University of Barcelona and Hospital Clínic-IDIBAPS published a review article in the journal Nature Cancer in which they describe the molecular alterations observed in the evolution of the hepatocellular carcinoma –the most common type of liver cancer– and propose a sequencing strategy for systemic treatment incorporating all the approved therapies to date.
The article was coordinated by Josep M. Llovet, professor at the Faculty of Medicine and Health Sciences of the UB and ICREA professor at IDIBAPS, where he leads the Translational Research Group in Hepatic Oncology. Llovet is the director of the Liver Cancer Program at the Icahn School of Medicine at Mount Sinai (New York). Rose Pinyol, tenure-track 1 lecturer at the Faculty of Medicine and Health Sciences of the UB and the mentioned group at IDIBAPS, also took part in the paper.
Hepatocellular carcinoma (HCC) accounts for more than 90% of the liver cancer cases –with a growing incidence worldwide– and is the second cause of death due to cancer. The life expectancy of patients with this cancer has improved thanks to the implementation of immunotherapy and targeted therapies.
Although the main molecular characteristics of HCC have been identified and the immune classes have been defined –which indicate whether a tumour will respond to immunotherapy–, only 25% of the tumours have a target therapy for which treatment is available.
The advanced hepatocellular carcinoma is resistant to chemotherapy and radiotherapy, which limits the therapeutic options. In 2007, the approval of sorafenib –the first systemic treatment for HCC– radically changed the patients’ perspective. Since then, different first and second-line systemic treatments have been approved.
A new era in the treatment of hepatocellular carcinoma
In 2020, the treatment of this disease based on the use of immunotherapy combinations started a new phase. This was due to the superiority of the combination of atezolizumab (PD-L1 inhibitor that boosts the immune system’s ability to attack cancer cells) with bevacizumab (inhibitor that slows down the formation of new blood vessels), over sorafenib, regarding the patient’s survival and the progression-free time.
In this review, the team provides with an integrated description of the molecular mechanisms that define the origin and evolution of HCC, as well as the oncogenic drivers and the molecular and immune classes. They also evaluated the latest advances and the approval of other molecular and immune systemic treatments, and provide with a new therapeutic scheme that includes all the current available drugs and their sequencing.
“Moreover, we assess how this knowledge can be transferred to precision oncology providing a perspective on the role of HCC systemic therapies in the management of the disease and the transition from local-regional to systemic treatments. Finally, we are proposing a new sequencing scheme for systemic treatment which integrates all the currently approved drugs and the hierarchy of their use”, notes Josep M. Llovet.
The article also gathers existing evidence on new molecular treatments and immunotherapy in early stages of clinical trials to contribute to clinical decision-making, as well as information on new clinical trials with biomarkers and trial design for future research.
Llovet, J. M.; Pinyol, R.; Kelley, R. K.; El-Khoueiry, A.; Reeves, H. L.; Wang, X. W.; Gores, G. J.; Villanueva, A. «Molecular pathogenesis and systemic therapies for hepatocellular carcinoma». Nature Cancer, April 2022. Doi: 10.1038/s43018-022-00357-2