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Why does survival of hepatocellular carcinoma patients remain so low? Key stumbling blocks and questions in preclinical and clinical development
Margherita Rimini
, Nicole Liscia
, Valentina Burgio
& Andrea Casadei-Gardini
Received 08 Feb 2022, Accepted 10 Mar 2022, Accepted author version posted online: 11 Mar 2022
Download citation https://doi.org/10.1080/13543784.2022.2053108 CrossMark Logo CrossMark
Accepted author version
ABSTRACT
INTRODUCTION
: Hepatocellular carcinoma (HCC) is a complex disease which involves diverse molecular pathways and etiologies. In recent years, several new systemic treatments have improved survival in advanced stage disease, but numerous significant challenges remain. No significant improvements have been achieved in the intermediate stage disease; this may be attributed to the difficulties in stratification of patients and the broad spectrum of clinical situations in terms of tumor burden and liver function.
AREAS COVERED
: This article considers the recent progress in first- and second-line therapy for advanced HCC. Investigational strategies conducted in intermediate stage HCC, which involve mainly combination therapy with locoregional approaches and systemic drugs, antiangiogenics, immunotherapies (or both), are then examined. Later, the paper offers insights on the questions and challenges that lie ahead for treating HCC.
EXPERT OPINION
Clinical and biomolecular markers for the stratification of patients are needed for therapeutic progress. Further molecular profiling data could enhance our knowledge of the molecular pathways underlying this tumor and facilitate the identification of targetable aberrations. This could offer opportunities for precision medicine approaches and improved survival.
KEYWORDS: Hepatocellular carcinomasystemic therapylocoregional treatmentcombination therapyantiangiogenic drugsimmunotherapybiomarkersclinical trials
Disclaimer
As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.
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ARTICLE HIGHLIGHTS
Randomized trials have led to the approval of numerous systemic treatments for advanced HCC; these include tyrosine kinase inhibitors (TKIs), immunotherapies, and combination approaches.
The identification of clinical and biomolecular markers for the selection of patients more likely to respond to a specific treatment is an urgent need and a challenge.
Intermediate stage HCC is characterized by a significant heterogeneity in terms of tumor burden and liver function, so improving the selection of patients for specific treatments is desirable in this setting.
Several promising combinations which involve locoregional and systemic treatments (antiangiogenic drugs and immunotherapies) are under investigation and may yield a survival improvement for intermediate stage HCC patients.
Further next generation sequencing studies will better define the molecular landscape of HCC which could open up opportunities for precision-based medicine. |
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发表于 2022-3-12 21:36