The metabolic and toxicological considerations for mTOR inhibitors in the treatment of hepatocarcinoma

Veronica Ojetti, Antonio Gasbarrini, Francesca Romana Ponziani, Annalisa Tortora, Luca Di Maurizio, Flaminia Purchiaroni

Risultato della ricerca: Contributo in rivistaArticolo in rivista

5 Citazioni (Scopus)

Abstract

INTRODUCTION: Hepatocellular carcinoma (HCC) is a major health problem worldwide. Several molecular pathways involved in HCC growth and progression have recently been identified. Rapamycin analogs are able to inhibit one of the most active oncogenic molecular pathways in HCC cells: the mammalian target of rapamycin (mTOR) pathway. AREAS COVERED: In this review, the authors analyze the principal molecular features of the mTOR pathway and the use of rapamycin analogs in the treatment of hepatocarcinoma. The article also looks at the reoccurrence of HCC following liver transplantation as well as after the treatment of de novo neoplasms. Finally, the authors discuss the advantage of using a combined HCC pharmacological therapy to obtain a synergistic effect on tumor mass. EXPERT OPINION: Among the available options for the treatment of advanced-stage HCC, mTOR pathway inhibitors show great promise. Once these agents have their safety and efficacy confirmed, in the treatment of liver disease, their use should be considered in patients affected by HCC. This should especially be the case for those who have had liver transplants or suffered with de novo tumors. Moreover, the authors believe that mTOR inhibitors could be used in a combined pharmacological approach to improve HCC molecular-targeted therapy by producing a multiple-level block of tumor intracellular signaling.
Lingua originaleEnglish
pagine (da-a)1535-1546
Numero di pagine12
RivistaEXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume7
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Animals
  • Carcinoma, Hepatocellular
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors
  • Humans
  • Liver Neoplasms
  • Liver Transplantation
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Signal Transduction
  • Sirolimus
  • TOR Serine-Threonine Kinases

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