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mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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Development and Application of Rapamycin-regulated Tyrosine Phosphatases
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Pilot study: rapamycin in advanced hepatocellular carcinoma.

M Schöniger-Hekele1, C Müller

  • 1Klinik Innere Medizin III, Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien, Vienna, Austria. maximilian.schoeniger-hekele@meduniwien.ac.at

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Rapamycin therapy was well tolerated in patients with advanced hepatocellular carcinoma (HCC), but showed minimal effectiveness in tumor response and survival. Further research into mTOR inhibitors for HCC is warranted.

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Area of Science:

  • Oncology
  • Pharmacology
  • Hepatology

Background:

  • The PI3K/Akt/mTOR pathway plays a role in liver cancer development.
  • Rapamycin, an mTOR inhibitor, causes cell cycle arrest and is explored as a cancer treatment adjuvant.

Purpose of the Study:

  • To evaluate the safety and tolerability of rapamycin in patients with advanced hepatocellular carcinoma (HCC).

Main Methods:

  • A study included 18 patients with advanced HCC ineligible for standard therapies between June 2005 and February 2007.
  • Patients had compensated liver cirrhosis (Child A/B/C) and confirmed HCC, with most at advanced BCLC stages C and D.

Main Results:

  • Rapamycin treatment was generally well-tolerated, with the most frequent side effects being thrombocytopenia and anemia.
  • No tumor responses were observed; median overall survival was 5.27 months, and median time to progression was 3 months.

Conclusions:

  • Rapamycin demonstrates good tolerability in advanced HCC patients.
  • However, rapamycin exhibits limited efficacy in treating advanced HCC.