Cited by 16Hepatocellular Carcinoma Treatment and PrognosisPI3K/AKT/mTOR signaling in cancerLiver Disease Diagnosis and Treatment

NAFLD-associated hepatocellular carcinoma (HCC) – A compelling case for repositioning of existing mTORc1 inhibitors

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Sharma, Nutan, Singh, Lakhwinder, Sharma, Aditya, Kumar, Ajay, Mahajan, Dinesh·2024·Pharmacological Research

Abstract

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) is a growing concern for the high incidence rate of hepatocellular carcinoma (HCC) globally. The progression of NAFLD to HCC is heterogeneous and non-linear, involving intermediate stages of non-alcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. There is a high unmet clinical need for appropriate diagnostic, prognostic, and therapeutic options to tackle this emerging epidemic. Unfortunately, at present, there is no validated marker to identify the risk of developing HCC in patients suffering from NAFLD or NASH. Additionally, the current treatment protocols for HCC don't differentiate between viral infection or NAFLD-specific etiology of the HCC and have a limited success rate. The mammalian target of rapamycin complex 1 (mTORc1) is an important protein involved in many vital cellular processes like lipid metabolism, glucose homeostasis, and inflammation. These cellular processes are highly implicated in NAFLD and its progression to severe liver manifestations. Additionally, hyperactivation of mTORc1 is known to promote cell proliferation, which can contribute to the genesis and progression of tumors. Many mTORc1 inhibitors are being evaluated for different types of cancers under various phases of clinical trials. This paper deliberates on the strong pathological implication of the mTORc1 signaling pathway in NAFLD and its progression to NASH and HCC and advocates for a systematic investigation of known mTORc1 inhibitors in suitable pre-clinical models of HCC having NAFLD/NASH-specific etiology.

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Crossref · 10.1016/j.phrs.2024.107375

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Authors
Sharma, N., Singh, L., Sharma, A., Kumar, A., & Mahajan, D.
Affiliations
Translational Health Science and Technology Institute (IN)
Corresponding author
Mahajan, Dinesh
Venue
Pharmacological Research
Publisher
Elsevier BV
Published
2024-10
Volume
208
Pages
107375
ISSN
1043-6618 (ISSN-L)
OpenAlex
W4402059392
Cited by
16
References
162
Citations by year
2026: 5 · 2025: 11
FWCI
1.15
Type
journal article
Language
en
Open access
Locations
  • Pharmacological Research (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Science and Engineering Research Board (TAR/2021/000189)
  • Department of Science and Technology, Ministry of Science and Technology, India
  • Department of Biotechnology
  • Biotechnology Industry Research Assistance Council (BT/AIR01362/PACE-22/20)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
non-alcoholic fatty liver disease, hepatocellular carcinoma, mTORC1 inhibitors, nonalcoholic steatohepatitis, liver fibrosis, liver cirrhosis, mTOR signaling, drug repurposing, tumor progression
MeSH terms
Mechanistic Target of Rapamycin Complex 1, MTOR Inhibitors, Animals, Antineoplastic Agents, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Signal Transduction, Drug Repositioning, Non-alcoholic Fatty Liver Disease

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