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<p>Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer which ranks as third leading cause of cancer-related death worldwide. There are various pathological conditions that lead to development and progression of HCC. Barcelona clinic liver cancer (BCLC) system classifies HCC into very early, early, intermediate, advanced and terminal stages. Most of the HCC cases are identified at later stages for which treatment options is very limited. HCC can be managed when it is diagnosed at an earlier stage, which majorly depends on the robust biomarkers for diagnosis and prognosis. This review highlights key established biomarkers for HCC and introduces emerging biomarkers such as CDC20, CDK1, and AURKA—which are markedly overexpressed in HCC and have potential as early diagnostic and treatment&#xa0;targets. Along with their possible clinical implications, the mechanisms behind their dysregulation in HCC are reviewed. The review provides information on a variety of phytochemicals that target CDK1, such as alkaloids, flavonoids, glycosides, guanidine, lactones, phenols, purines, quinones, saponins, tannins, terpenes, and plant extracts. By means of mechanisms such as G2/M phase cell cycle arrest, apoptosis induction, autophagy modification, and angiogenesis suppression, flavonoid-class drugs notably demonstrate anti-cancer activities against HCC. Furthermore, small molecule inhibitors that target CDK1 and AURKA have shown promise as therapeutics for the treatment of HCC.&#xa0;Despite these developments, there is still a significant research void in this field due to the lack of CDC20 studies. In addition to highlighting the need for more research on CDC20's involvement in HCC, this study offers a fresh viewpoint by fusing the development of biomarkers with small molecules and&#xa0;phytochemical-based treatment approaches. This study also&#xa0;provides new insights into the future of precision oncology by linking these disciplines and laying the foundation for creative methods of early HCC detection and therapy.</p> Graphical Abstract <p></p>

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A comprehensive review of targeting early-stage biomarkers by small molecules and phytochemicals in hepatocellular carcinoma

  • 期刊论文

  • 发表日期：

    2025年8月8日

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  • Suryaa Manoharan,
  • Ilakkiya Govindaraju,
  • Viswaganesh Venkatesan,
  • Ekambaram Perumal

摘要

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer which ranks as third leading cause of cancer-related death worldwide. There are various pathological conditions that lead to development and progression of HCC. Barcelona clinic liver cancer (BCLC) system classifies HCC into very early, early, intermediate, advanced and terminal stages. Most of the HCC cases are identified at later stages for which treatment options is very limited. HCC can be managed when it is diagnosed at an earlier stage, which majorly depends on the robust biomarkers for diagnosis and prognosis. This review highlights key established biomarkers for HCC and introduces emerging biomarkers such as CDC20, CDK1, and AURKA—which are markedly overexpressed in HCC and have potential as early diagnostic and treatment targets. Along with their possible clinical implications, the mechanisms behind their dysregulation in HCC are reviewed. The review provides information on a variety of phytochemicals that target CDK1, such as alkaloids, flavonoids, glycosides, guanidine, lactones, phenols, purines, quinones, saponins, tannins, terpenes, and plant extracts. By means of mechanisms such as G2/M phase cell cycle arrest, apoptosis induction, autophagy modification, and angiogenesis suppression, flavonoid-class drugs notably demonstrate anti-cancer activities against HCC. Furthermore, small molecule inhibitors that target CDK1 and AURKA have shown promise as therapeutics for the treatment of HCC. Despite these developments, there is still a significant research void in this field due to the lack of CDC20 studies. In addition to highlighting the need for more research on CDC20's involvement in HCC, this study offers a fresh viewpoint by fusing the development of biomarkers with small molecules and phytochemical-based treatment approaches. This study also provides new insights into the future of precision oncology by linking these disciplines and laying the foundation for creative methods of early HCC detection and therapy.

Graphical Abstract