|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Therapeutic inhibition of mammalian target of rapamycin (mTOR) in cancer is complicated by the existence of a negative feedback loop linking mTOR to the phosphatidylinositol 3-kinase (PI3K)-Akt pathway.
|
19435890 |
2009 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
We tested the hypothesis that IGF1R up-regulation mediates resistance to cancer therapeutics, evaluating the effects of IGF1R depletion on sensitivity to cytotoxic drugs, which are ineffective in RCC, and the mammalian target of rapamycin (mTOR) inhibitor rapamycin, analogues of which have clinical activity in this tumor.
|
19509240 |
2009 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Clinical trials of these analogs have already validated the importance of mTOR inhibition as a novel treatment strategy for several malignancies.
|
19963098 |
2009 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
These studies demonstrate a novel mouse model of IBD-colorectal cancer progression in which disrupted immune regulation, mTOR-Stat3 signaling, and epithelial hyperproliferation are integrated and simultaneously linked to the development of malignancy.
|
20042677 |
2010 |
|
Malignant Neoplasms
|
0.400 |
AlteredExpression
|
group |
BEFREE |
Here, we discuss the case history of the discovery and properties of an increasingly used chemical probe, the pan-class I PI3K and mammalian target of rapamycin (mTOR) inhibitor PI-103 (a pyridofuropyrimidine), and its very recent evolution into the thienopyrimidine drug GDC-0941, which exhibits excellent oral anticancer activity in preclinical models and is now undergoing phase I clinical trials in cancer patients.
|
20179189 |
2010 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Mammalian target of rapamycin (mTOR) inhibitors such as rapamycin have shown modest effects in cancer therapy due in part to the removal of a negative feedback loop leading to the activation of the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathway.
|
20392999 |
2010 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
A key target of PA is the mammalian target of rapamycin (mTOR), a serine-threonine kinase that has been widely implicated in cancer cell survival signals.
|
20438709 |
2010 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
We evaluate genetic variation in nine genes in a candidate pathway as follows: STK11 (3 tagSNPs), PTEN (9 tagSNPs), FRAP1 (mTOR) (4 tagSNPs), TSC1 (14 tagSNPs), TSC2 (8 tagSNPs), Akt1 (2 tagSNPs), PIK3CA (7 tagSNPs), PRKAA1 (13 tagSNPs) and PRKAG2 (68 tagSNPs) in two population-based case-control studies of colon (n = 1574 cases, 1940 controls) and rectal (n = 91 cases, 999 controls) cancer.
|
20622004 |
2010 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
These data suggest that mTOR inhibitors currently in use will be ineffective against cancers that have a mutation in either KRAS or BRAF despite having PI3K/AKT/mTOR pathway activation.
|
20664174 |
2010 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
In cancer therapy novel concepts focus on phosphoinositide 3-kinase (PI3K)/activated protein kinase B (p-AKT)/mammalian target of rapamycin (mTOR) inhibitors.
|
20844931 |
2010 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Cancer cell survival following DNA damage-mediated premature senescence is regulated by mammalian target of rapamycin (mTOR)-dependent Inhibition of sirtuin 1.
|
21471201 |
2011 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Taken together, these findings in our study suggest that induction of mTOR-dependent autophagic and apoptotic cell death may be an important mechanism in cancer chemotherapy by ISL.
|
21956714 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
However, there is reason for renewed optimism given the now very detailed knowledge of the cancer genome in GBM and a wealth of novel compounds entering the clinic, including next generation RTK inhibitors, class I PI3K inhibitors, mTOR kinase inhibitors (TORKinibs), and dual PI3(K)/mTOR inhibitors.
|
22015553 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
The mammalian target of rapamycin (mTOR) plays crucial roles in proliferative and antiapoptotic signaling in lymphoid malignancies.
|
22080480 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Inhibition of mTOR is an established therapeutic principle in transplantation medicine and in cancers, such as renal cell carcinoma.
|
22125056 |
2012 |
|
Malignant Neoplasms
|
0.400 |
GeneticVariation
|
group |
BEFREE |
Two classes of mTOR inhibitors are currently being evaluated as cancer therapeutics: rapamycin and its analogs, which partially inhibit mTORC1 and in some cell types mTORC2, and the recently described ATP-competitive inhibitors, which inhibit the kinase activity of both complexes.
|
22125076 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Hyperactivation of the mTOR protein has been linked to development of cancer, raising mTOR as an attractive target for cancer therapy.
|
22155350 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Mammalian target of rapamycin (mTOR) inhibitors have been clinically used as anticancer agents in several types of human malignancies including neuroendocrine tumor (NET) but the development of clinical resistances or their therapeutic limitations have been also reported.
|
22178087 |
2012 |
|
Malignant Neoplasms
|
0.400 |
AlteredExpression
|
group |
BEFREE |
Alterations in Akt and mTOR activity have been linked to the progression of multiple diseases such as cancer and type 2 diabetes.
|
22354785 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer.
|
22367541 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Mammalian target of rapamycin (mTOR) is an evolutionarily conserved protein kinase. mTOR forms two distinct functional multiprotein kinase complexes that mutually phosphorylate different substrates and regulate a wide array of essential cellular processes including translation, transcription and autophagy. mTOR is active in several types of cancer and plays a role in a variety of other serious human diseases, including diabetes, neurodegenerative disorders and polycystic kidney disease.
|
22388550 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Mammalian target of rapamycin complex 1 (mTORC1) signaling is frequently dysregulated in cancer.
|
22474287 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Furthermore, three independent laboratories including our own have demonstrated that the stability of DEPTOR is controlled by the SCF(β-TrCP) E3 ubiquitin ligase and deregulated DEPTOR destruction might contribute to hyperactivation of mTOR in pathologic conditions including cancer.
|
22745583 |
2012 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
The mechanistic target of rapamycin (mTOR) kinase controls growth and metabolism, and its deregulation underlies the pathogenesis of many diseases, including cancer, neurodegeneration, and diabetes. mTOR complex 1 (mTORC1) integrates signals arising from nutrients, energy, and growth factors, but how exactly these signals are propagated await to be fully understood.
|
22749019 |
2012 |
|
Malignant Neoplasms
|
0.400 |
AlteredExpression
|
group |
BEFREE |
These results show the use of credentialed murine models for large-scale efficacy testing of diverse anticancer regimens and predict that combinations of PI3K/mTOR and MEK inhibitors will show antitumor activity in a wide range of human malignancies.
|
22872574 |
2012 |