In the majority of solid tumors examined, including bladder, brain, breast, colon, ovarian, pancreatic, prostate, and renal carcinomas, nuclear expression of HIF-1alpha and -2alpha was observed in varying subsets of the tumor cells.
Characterization of the metabolic intermediates and the corresponding metabolic pathways altered by HIF-1α would facilitate the identification of therapeutic targets for hypoxic microenvironments prevalent in pancreatic ductal adenocarcinoma and other solid tumors.
This work suggests that mitochondria-targeting metabolic modulators that increase pyruvate dehydrogenase activity, in addition to the recently described pro-apoptotic and anti-proliferative effects, suppress angiogenesis as well, normalizing the pseudo-hypoxic signals that lead to normoxic HIF1α activation in solid tumors.
Hypoxia and signaling via hypoxia-inducible factor-1 (HIF-1) is a key feature of solid tumors and is related to tumor progression as well as treatment failure.
2-Methoxyestradiol (2ME2) is a natural compound with HIF-1alpha inhibitory activity that is currently being evaluated in phase 1 and 2 clinical trials for advanced solid tumors and multiple myeloma.
All of these results indicate that Akt/mTOR-dependent translation of HIF-1alpha plays a critical role in the postirradiation up-regulation of intratumoral HIF-1 activity in response to radiation-induced alterations of glucose and oxygen availability in a solid tumor.
It is reasonable to speculate that down-regulation of HIF-1alpha activity could be a potential mechanism useful to prevent survival or angiogenic activity of various solid tumors.
Hypoxia is a common phenomenon in the development of solid tumors, and hypoxia inducible factor 1 (HIF-1) plays a central role in coordinating the cellular response to hypoxia and in oxygen homeostasis.
The identification of HIF1A targets expressed in both normoxia and hypoxia and of HIF1A/hypoxia signatures might meliorate the prognostic stratification and therapeutic successes in patients with high-risk solid tumors.
Hypoxia-inducible factor-1 (HIF-1) is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia, a common feature of the microenvironment in solid tumors.
The adaptation of solid tumors to the low oxygen/nutrient environment is mediated by the pivotal transcription role of hypoxia-inducible factor-1 (HIF-1).
Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that directly transactivates genes important for the growth and metabolism of solid tumors.
Hypoxia is the hallmark of solid tumors and contributes to tumor angiogenesis mainly through activation of the transcription factor hypoxia-inducible factor-1 (HIF-1).
Hypoxia-inducible factor 1 (HIF-1) controls angiogenesis and glycolysis, two leading characteristics of solid tumor invasion, metastasis, and lethality.