Current discovery strategies for hepatocellular carcinoma therapeutics
Qiuzi Dai1,2,3, Cunlong Zhang3,4, Zigao Yuan2,3,4
1Department of Chemistry, Tsinghua University, Beijing, PR China.
Abstract:
Introduction: The global incidence of hepatocellular carcinoma (HCC) is not expected to decline significantly over the next 30 years. And although the latest gene sequencing studies have established its genetic map, the potentially targetable drivers of HCC are, so far, difficult to identify. To date, only seven drugs have been approved by the FDA for unresectable HCC treatment; thus, effective therapeutic breakthroughs are still needed urgently.Areas covered: In this review, the authors discuss both genetic and epigenetic alterations in HCC and introduce the current progress with some of the representative molecular targeting inhibitors, listing some of the approved drugs for the targets of HCC. The structure-activity relationship of molecules (e.g. thalidomide, bortezomil) used for HCC is also discussed.Expert opinion: Effective therapeutic targets and effective drugs for HCC treatment are an urgent unmet need. Better understanding and characterization of genetic and epigenetic alterations, which are important to hepatocarcinogenesis, may help to understand the molecular pathogenesis of HCC, as well as provide novel therapeutic lead compounds for HCC treatment.
Insights
Hepatocellular carcinoma (HCC) treatment needs breakthroughs. This review covers genetic/epigenetic alterations and molecular inhibitors, highlighting the urgent need for novel therapeutic targets and drugs for this challenging cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) incidence remains high globally, with limited targeted therapies.
- Despite advances in genetic mapping, identifying actionable drivers for HCC has been challenging.
- Currently, only seven FDA-approved drugs exist for unresectable HCC, underscoring the need for new treatments.
Purpose of the Study:
- To review genetic and epigenetic alterations in HCC.
- To discuss current molecular targeting inhibitors and approved drugs for HCC.
- To explore structure-activity relationships of relevant molecules.
Main Methods:
- Literature review of genetic and epigenetic alterations in HCC.
- Analysis of molecular targeting inhibitors and their approved applications.
- Discussion of structure-activity relationships of molecules like thalidomide and bortezomil.
Main Results:
- Detailed overview of genetic and epigenetic changes driving hepatocarcinogenesis.
- Identification of representative molecular targeting inhibitors and their targets in HCC.
- Exploration of specific drug examples and their molecular properties.
Conclusions:
- Understanding genetic and epigenetic alterations is crucial for HCC pathogenesis.
- Novel therapeutic targets and effective drugs for HCC are urgently required.
- Further research into molecular pathogenesis may yield new therapeutic compounds.
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