Limits...
Hypoxia-inducible factor-1 as a therapeutic target in endometrial cancer management.

Seeber LM, Zweemer RP, Verheijen RH, van Diest PJ - Obstet Gynecol Int (2010)

Bottom Line: Therefore, HIF-1 could be an attractive therapeutic target.Selective HIF-1 inhibitors have not been identified.A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1alpha protein levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynaecological Oncology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.

ABSTRACT
In the Western world, endometrial cancer (EC) is the most common malignant tumor of the female genital tract. Solid tumors like EC outgrow their vasculature resulting in hypoxia. Tumor hypoxia is important because it renders an aggressive phenotype and leads to radio- and chemo-therapy resistance. Hypoxia-inducible factor-1alpha (HIF-1alpha) plays an essential role in the adaptive cellular response to hypoxia and is associated with poor clinical outcome in EC. Therefore, HIF-1 could be an attractive therapeutic target. Selective HIF-1 inhibitors have not been identified. A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1alpha protein levels. In clinical trials for the treatment of advanced and/or recurrent EC are the topoisomerase I inhibitor Topotecan, mTOR-inhibitor Rapamycin, and angiogenesis inhibitor Bevacizumab. Preliminary data shows encouraging results for these agents. Further work is needed to identify selective HIF-1 inhibitors and to translate these into clinical trials.

No MeSH data available.


Related in: MedlinePlus

Mechanisms of HIF activation in cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2821774&req=5

fig1: Mechanisms of HIF activation in cancer.

Mentions: A developing solid tumour will outgrow its own vasculature beyond the size of several cubic millimetres, resulting in hypoxia (defined as an oxygen tension below the physiological level, <2% pO2) [2]. Hypoxia has been found to be an important event in carcinogenesis as it renders a more aggressive phenotype with increased invasiveness and proliferation, formation of metastases, and poorer survival in several types of cancer [3, 4]. Furthermore, it has been shown that hypoxia-induces resistance to radiotherapy and chemotherapy [5–7]. The key survival gene for cells in a hypoxic environment is hypoxia inducible factor-1 (HIF-1) (see Figure 1).


Hypoxia-inducible factor-1 as a therapeutic target in endometrial cancer management.

Seeber LM, Zweemer RP, Verheijen RH, van Diest PJ - Obstet Gynecol Int (2010)

Mechanisms of HIF activation in cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2821774&req=5

fig1: Mechanisms of HIF activation in cancer.
Mentions: A developing solid tumour will outgrow its own vasculature beyond the size of several cubic millimetres, resulting in hypoxia (defined as an oxygen tension below the physiological level, <2% pO2) [2]. Hypoxia has been found to be an important event in carcinogenesis as it renders a more aggressive phenotype with increased invasiveness and proliferation, formation of metastases, and poorer survival in several types of cancer [3, 4]. Furthermore, it has been shown that hypoxia-induces resistance to radiotherapy and chemotherapy [5–7]. The key survival gene for cells in a hypoxic environment is hypoxia inducible factor-1 (HIF-1) (see Figure 1).

Bottom Line: Therefore, HIF-1 could be an attractive therapeutic target.Selective HIF-1 inhibitors have not been identified.A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1alpha protein levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynaecological Oncology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.

ABSTRACT
In the Western world, endometrial cancer (EC) is the most common malignant tumor of the female genital tract. Solid tumors like EC outgrow their vasculature resulting in hypoxia. Tumor hypoxia is important because it renders an aggressive phenotype and leads to radio- and chemo-therapy resistance. Hypoxia-inducible factor-1alpha (HIF-1alpha) plays an essential role in the adaptive cellular response to hypoxia and is associated with poor clinical outcome in EC. Therefore, HIF-1 could be an attractive therapeutic target. Selective HIF-1 inhibitors have not been identified. A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1alpha protein levels. In clinical trials for the treatment of advanced and/or recurrent EC are the topoisomerase I inhibitor Topotecan, mTOR-inhibitor Rapamycin, and angiogenesis inhibitor Bevacizumab. Preliminary data shows encouraging results for these agents. Further work is needed to identify selective HIF-1 inhibitors and to translate these into clinical trials.

No MeSH data available.


Related in: MedlinePlus