914083fd74e2c14586ca2a4a434b2bd9 pmc_34572344.pdf e3805af5ba872686b2b9a8b8d520067cbb8c03a7 pmc_34572344.pdf f40905e893d62c437bc256486ba9c831d008b2508c3630c26a61fdd24e613346 pmc_34572344.pdf Title: Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection Subject: Hepatocellular carcinoma has become a leading cause of cancer-associated mortality throughout the world, and is of great concern. Currently used chemotherapeutic drugs in the treatment of hepatocellular carcinoma lead to severe side effects, thus underscoring the need for further research to develop novel and safer therapies. Liver resection in cancer patients is routinely performed. After partial resection, liver regeneration is a perfectly calibrated response apparently sensed by the body’s required liver function. This process hinges on the effect of several growth factors, among other molecules. However, dysregulation of growth factor signals also leads to growth signaling autonomy and tumor progression, so control of growth factor expression may prevent tumor progression. This review describes the role of some of the main growth factors whose dysregulation promotes liver tumor progression, and are also key in regenerating the remaining liver following resection. We herein summarize and discuss studies focused on partial hepatectomy and liver carcinogenesis, referring to hepatocyte growth factor, insulin-like growth factor, and epidermal growth factor, as well as their suitability as targets in the treatment of hepatocellular carcinoma. Finally, and given that drugs remain one of the mainstay treatment options in liver carcinogenesis, we have reviewed the current pharmacological approaches approved for clinical use or research targeting these factors. Keywords: liver cancer; liver resection; growth factors; regeneration; hepatocyte growth factor; insulin-like growth factor-1; epidermal growth factor Author: Ana I. Álvarez-Mercado, Albert Caballeria-Casals, Carlos Rojano-Alfonso, Jesús Chávez-Reyes, Marc Micó-Carnero, Alfredo Sanchez-Gonzalez, Araní Casillas-Ramírez, Jordi Gracia-Sancho and Carmen Peralta Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Sep 8 07:32:52 2021 CEST ModDate: Wed Sep 8 07:40:33 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1999666 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RWSFOK+VnURWPalladioL Type 1 Custom yes yes no 10 0 JYTCJH+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 MHOGBS+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 XTDXIN+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 TAGTVB+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 QDULQU+EURM10 Type 1 Builtin yes yes no 87 0 AWQBBM+stmary9 Type 1 Builtin yes yes no 91 0 LYARHA+CMSY10 Type 1 Builtin yes yes no 95 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-22 02:46:00 CET RepresentationInformation: pmc_34572344.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-10-04 03:39:16 CEST Size: 1999666 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 606 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Growth Factors in Liver Tumorigenesis and Liver Regeneration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Hepatocyte Growth Factor (HGF) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Epidermal Growth Factor (EGF) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Insulin-Like Growth Factor-1 (IGF-1) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Hepatocyte Growth Factor, Insulin-Like Growth Factor and Epidermal Growth Factor and Their Link with Vascular Endothelial Growth Factor Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Pharmacological Approaches Targeting HGF, EGF and IGF-1 Approved for the Treatment of Liver Tumorigenesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Clinical Strategies in Liver Tumorigenesis and Liver Regeneration Based on Growth Factor Modulation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Other Drugs Blocking the HGF/c-Met Axis in Liver Tumorigenesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Pharmacological Approaches to Modulate EGF and IGF-1 Pathways in Liver Tumorigenesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Role of HGF, EGF and IGF-1 in Liver Hepatectomy: Implications of External Regulation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Concluding Remarks Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Info: Title: Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection Author: Ana I. Álvarez-Mercado, Albert Caballeria-Casals, Carlos Rojano-Alfonso, Jesús Chávez-Reyes, Marc Micó-Carnero, Alfredo Sanchez-Gonzalez, Araní Casillas-Ramírez, Jordi Gracia-Sancho and Carmen Peralta Subject: Hepatocellular carcinoma has become a leading cause of cancer-associated mortality throughout the world, and is of great concern. Currently used chemotherapeutic drugs in the treatment of hepatocellular carcinoma lead to severe side effects, thus underscoring the need for further research to develop novel and safer therapies. Liver resection in cancer patients is routinely performed. After partial resection, liver regeneration is a perfectly calibrated response apparently sensed by the body’s required liver function. This process hinges on the effect of several growth factors, among other molecules. However, dysregulation of growth factor signals also leads to growth signaling autonomy and tumor progression, so control of growth factor expression may prevent tumor progression. This review describes the role of some of the main growth factors whose dysregulation promotes liver tumor progression, and are also key in regenerating the remaining liver following resection. We herein summarize and discuss studies focused on partial hepatectomy and liver carcinogenesis, referring to hepatocyte growth factor, insulin-like growth factor, and epidermal growth factor, as well as their suitability as targets in the treatment of hepatocellular carcinoma. Finally, and given that drugs remain one of the mainstay treatment options in liver carcinogenesis, we have reviewed the current pharmacological approaches approved for clinical use or research targeting these factors. 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