Journal
CANCERS
Volume 12, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/cancers12051290
Keywords
HCC; obesity; NASH; genetic factors; epigenetic changes; therapeutics
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1R01DK107451-01A1]
- National Cancer Institute (NCI) [1R01CA230561-01A1, 1R01CA240004-01, 1R01CA244993-01]
- Department of Defense (DOD) Grant [CA170048]
- CDMRP [1100630, CA170048] Funding Source: Federal RePORTER
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Obesity is a global, intractable issue, altering inflammatory and stress response pathways, and promoting tissue adiposity and tumorigenesis. Visceral fat accumulation is correlated with primary tumor recurrence, poor prognosis and chemotherapeutic resistance. Accumulating evidence highlights a close association between obesity and an increased incidence of hepatocellular carcinoma (HCC). Obesity drives HCC, and obesity-associated tumorigenesis develops via nonalcoholic fatty liver (NAFL), progressing to nonalcoholic steatohepatitis (NASH) and ultimately to HCC. The better molecular elucidation and proteogenomic characterization of obesity-associated HCC might eventually open up potential therapeutic avenues. The mechanisms relating obesity and HCC are correlated with adipose tissue remodeling, alteration in the gut microbiome, genetic factors, ER stress, oxidative stress and epigenetic changes. During obesity-related hepatocarcinogenesis, adipokine secretion is dysregulated and the nuclear factor erythroid 2 related factor 1 (Nrf-1), nuclear factor kappa B (NF-kappa B), mammalian target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways are activated. This review captures the present trends allied with the molecular mechanisms involved in obesity-associated hepatic tumorigenesis, showcasing next generation molecular therapeutic strategies and their mechanisms for the successful treatment of HCC.
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