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Cancers 2013, 5(2), 320-333; doi:10.3390/cancers5020320
Review

Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas

 and
*
Anatomic Pathology, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, 6th Floor Founders Building, Philadelphia, PA 19104, USA
* Author to whom correspondence should be addressed.
Received: 23 January 2013 / Revised: 12 March 2013 / Accepted: 26 March 2013 / Published: 2 April 2013
(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)
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Abstract

Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression.
Keywords: soft tissue sarcoma; hypoxia; hypoxia-inducible factor; HIFs soft tissue sarcoma; hypoxia; hypoxia-inducible factor; HIFs
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Sadri, N.; Zhang, P.J. Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas. Cancers 2013, 5, 320-333.

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