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mTOR Signaling and Cancer Progression03:03

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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mTOR Signaling and Cancer Progression03:03

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Adaptive Mechanisms in Cancer Cells02:53

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Angiosarcoma: clinical and molecular insights.

Guy Lahat1, Asha R Dhuka, Hen Hallevi

  • 1Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Annals of Surgery
|May 21, 2010
PubMed
Summary
This summary is machine-generated.

Angiosarcoma (AS) is a rare cancer with poor outcomes. This study of 222 patients found localized AS has better survival than metastatic, and complete surgery improves prognosis. Molecular targets like the AKT/mTOR pathway warrant further investigation for new therapies.

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Area of Science:

  • Oncology
  • Sarcoma Research
  • Molecular Pathology

Background:

  • Angiosarcoma (AS) is a rare soft tissue sarcoma originating from endothelial cells.
  • Limited understanding of AS natural history and molecular drivers hinders therapeutic development.

Purpose of the Study:

  • To evaluate the natural history of angiosarcoma using the largest patient cohort reported.
  • To identify molecular alterations in AS with potential therapeutic relevance.

Main Methods:

  • Retrospective review of 222 AS patients treated between 1993 and 2007.
  • Univariable and multivariable analyses to determine prognostic factors.
  • Immunohistochemical analysis of an AS tissue microarray (68 specimens) for molecular markers.

Main Results:

  • Localized AS (80.6%) had significantly longer median survival (49 months) than metastatic AS (19.4%; 10 months).
  • Complete surgical resection correlated with significantly better outcomes in localized AS patients.
  • Tumor size (>5 cm) and epithelioid histology were independent adverse prognosticators.
  • Overexpression of VEGF-A, VEGF-C, p-AKT, p-4EBP1, and eIF4E was observed in AS.

Conclusions:

  • Angiosarcoma has a poor prognosis, with 5-year survival at only 53% even after complete resection.
  • The AKT/mTOR pathway is implicated in AS pathogenesis.
  • Further research into the AKT/mTOR pathway as a therapeutic target for AS is warranted.