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MTOR XRCC1 (1 - 2 of 2)
PMID: 19402072
Targeting mTOR in renal cell carcinoma.
The mammalian target of rapamycin (mTOR) is ... therapeutic target for advanced renal cell carcinoma (RCC), ...   (details)

MTOR XRCC1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 19402072

Targeting mTOR in renal cell carcinoma.
Source

Cancer (5/15/2009)

Abstract

Targeting mTOR in renal cell carcinoma. The mammalian target of rapamycin (mTOR) is clearly an important therapeutic target for advanced renal cell carcinoma (RCC), although its mechanisms of activation are not completely understood. In first-line treatment of patients who have both advanced RCC and multiple risk factors for short survival, temsirolimus improves overall survival (OS) compared with interferon. In patients whose tumors have progressed after sunitinib and/or sorafenib therapy, everolimus improves progression-free survival compared with placebo. Beyond the initial phase 3 studies demonstrating efficacy, many important questions remain in the clinical application of mTOR inhibition and in developing other inhibitors of PI3K/Akt/mTOR signaling. Important objectives of current and future clinical investigations include a more detailed description of the molecular pathology of RCC and identification of potential biomarkers that are predictive of tumor sensitivity to PI3K/Akt/mTOR targeted therapies. This information may identify other groups of RCC patients that are likely to benefit from inhibition of this signaling pathway. Additional questions concern mechanisms by which tumors become resistant to mTOR inhibitor therapy and how such resistance can be defeated. Possible mechanisms include the loss of feedback inhibition of insulin receptor substate/PI3K signaling resulting from the inhibition of mTOR complex 1 by rapamycin analogs and the activating phosphorylation of Akt by mTOR complex 2. Laboratory studies indicate that these resistance mechanisms could be countered by using other targeted agents in combination with mTOR inhibitors.

PMID: 21075312
FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis.
mTORC1 is ... therapeutic target for renal cell carcinoma (RCC).   (details)

MTOR XRCC1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Cause:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 21075312

FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis.
Source

Cancer cell (11/16/2010)

Abstract

FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. mTORC1 is a validated therapeutic target for renal cell carcinoma (RCC). Here, analysis of Tsc1-deficient (mTORC1 hyperactivation) mice uncovered a FoxO-dependent negative feedback circuit constraining mTORC1-mediated renal tumorigenesis. We document robust FoxO activation in Tsc1-deficient benign polycystic kidneys and FoxO extinction on progression to murine renal tumors; murine renal tumor progression on genetic deletion of both Tsc1 and FoxOs; and downregulated FoxO expression in most human renal clear cell and papillary carcinomas, yet continued expression in less aggressive RCCs and benign renal tumor subtypes. Mechanistically, integrated analyses revealed that FoxO-mediated block operates via suppression of Myc through upregulation of the Myc antagonists, Mxi1-SRa and mir-145, establishing a FoxO-Mxi1-SRa/mir-145 axis as a major progression block in renal tumor development.