The advanced development of molecular targeted therapy for hepatocellular carcinoma

Yan, Tao; Yu, Lingxiang; Zhang, Ning; Peng, C. H. Lee; Su, Guodong; Jing, Yi; Zhang, Linzhi; Wu, Tong; Cheng, Jiamin; Guo, Qian; Shi, Xiaoliang; Lu, Yinying

doi:10.20892/j.issn.2095-3941.2021.0661

Cited by 27 publications

(18 citation statements)

References 158 publications

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“…Considering the heterogeneity of HCC, we calculated an accurate CRGPI score for every patient to guide personalized therapy and divided patients into two subgroups according to the median score as a cutoff value ( 46 , 47 ). The CRGPI signature was constructed based on 4 genes (FDX1, CDKN2A, DLAT, and LIAS).…”

Section: Discussionmentioning

confidence: 99%

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma

Liu

et al. 2022

Front. Immunol.

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Cuproptosis is a novel form of cell death, correlated with the tricarboxylic acid (TCA) cycle. However, the metabolic features and the benefit of immune checkpoint inhibitor (ICI) therapy based on cuproptosis have not yet been elucidated in Hepatocellular carcinoma (HCC). First, we identified and validated three cuproptosis subtypes based on 10 cuproptosis-related genes (CRGs) in HCC patients. We explored the correlation between three cuproptosis subtypes and metabolism-related pathways. Besides, a comprehensive immune analysis of three cuproptosis subtypes was performed. Then, we calculated the cuproptosis-related gene prognostic index (CRGPI) score for predicting prognosis and validated its predictive capability by Decision curve analysis (DCA). We as well explored the benefit of ICI therapy of different CRGPI subgroups in two anti-PD1/PD-L1 therapy cohorts (IMvigor210 cohort and GSE176307). Finally, we performed the ridge regression algorithm to calculate the IC50 value for drug sensitivity and Gene set enrichment analysis (GSEA) analysis to explore the potential mechanism. We found that cluster A presented a higher expression of FDX1 and was correlated with metabolism, glycolysis, and TCA cycle pathways, compared with the other two clusters. HCC patients with high CRGPI scores had a worse OS probability, and we further found that the CRGPI-high group had high expression of PD1/PDL1, TMB, and better response (PR/CR) to immunotherapy in the IMvigor210 cohort and GSE176307. These findings highlight the importance of CRGPI serving as a potential biomarker for both prognostic and immunotherapy for HCC patients. Generally, our results provide novel insights about cuproptosis into immune therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma

Liu

et al. 2022

Front. Immunol.

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“…Modern drug discovery begins with target identification. Various approaches at the crossroads such as structural biology, molecular biology, cell biology, genomics, proteomics, computational biology, and bioinformatics [ 39 , 40 , 41 , 42 , 43 , 44 , 45 ] are being explored to identify the target or related targets and investigate the pathogenesis. Understanding the pathogenesis is also vital for drug discovery and therapies.…”

Section: Computational Biology In Drug Designmentioning

confidence: 99%

Application of Computational Biology and Artificial Intelligence in Drug Design

Zhang

Luo

et al. 2022

IJMS

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Traditional drug design requires a great amount of research time and developmental expense. Booming computational approaches, including computational biology, computer-aided drug design, and artificial intelligence, have the potential to expedite the efficiency of drug discovery by minimizing the time and financial cost. In recent years, computational approaches are being widely used to improve the efficacy and effectiveness of drug discovery and pipeline, leading to the approval of plenty of new drugs for marketing. The present review emphasizes on the applications of these indispensable computational approaches in aiding target identification, lead discovery, and lead optimization. Some challenges of using these approaches for drug design are also discussed. Moreover, we propose a methodology for integrating various computational techniques into new drug discovery and design.

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“…Lenvatinib has been approved as a first-line treatment for advanced HCC, and regorafenib is recommended as a second-line treatment in patients with disease progression after sorafenib treatment. Cabozantinib is also used as an alternative second-line treatment 3 . Although these anti-angiogenic therapies are widely prescribed in HCC treatment, and some benefits have been noted, the survival benefits conferred by these anti-angiogenic therapies are modest 4 .…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies

Yao

Kong

et al. 2023

Cancer Biol Med

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Angiogenesis, the process of formation of new blood vessels, is required for cancer cells to obtain nutrients and oxygen. HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth, progression, invasion, and metastasis. Current anti-angiogenic therapies target mainly tyrosine kinases, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR), and are considered effective strategies for HCC, particularly advanced HCC. However, because the survival benefits conferred by these anti-angiogenic therapies are modest, new anti-angiogenic targets must be identified. Several recent studies have determined the underlying molecular mechanisms, including pro-angiogenic factors secreted by HCC cells, the tumor microenvironment, and cancer stem cells. In this review, we summarize the roles of pro-angiogenic factors; the involvement of endothelial cells, hepatic stellate cells, tumor-associated macrophages, and tumor-associated neutrophils present in the tumor microenvironment; and the regulatory influence of cancer stem cells on angiogenesis in HCC. Furthermore, we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC. A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

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The advanced development of molecular targeted therapy for hepatocellular carcinoma

Cited by 27 publications

References 158 publications

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma

Application of Computational Biology and Artificial Intelligence in Drug Design

Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies

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