Renal cell carcinoma (RCC)

Disease · 6 studies in the Atlas

Cancer of the kidney; target indication for everolimus treatment in clinical practice.

A kidney cancer treated with these drugs. The most common form of kidney cancer. It's an approved use for the mTOR-blocking drug everolimus in clinical practice.

Temsirolimus (ARCC) and everolimus (RECORD-1) both improved outcomes; exceptional responders have been traced to TSC1 loss.

TL;DR. Renal cell carcinoma (RCC) appears in 6 curated studies in Oliver's mTOR Atlas: 3 in people (3 human studies); 2 in animal models; 1 review. It has 3 interactions in the curated pathway model.

In the pathway model

3 interactions in the curated mTOR pathway model. Each row is a claim with the evidence behind it; the evidence code is the kind of study, not its quality.

Interaction	Mechanism	Evidence	Studies
Everolimus inhibits Renal cell carcinoma (RCC) mechanism: clinical-outcome · this link in full · on the map table	In a clinical trial, everolimus roughly doubled the time before advanced kidney cancer got worse, after other treatments had stopped working.RECORD-1: everolimus roughly doubled progression-free survival after other targeted therapy failed. Holds under: Second-line setting, after VEGF-targeted therapy - not first-line. shown in people · settled in the literature	H	MOT2008
mTORC1 associated-with Renal cell carcinoma (RCC) mechanism: association · this link in full · on the map table	Many kidney cancers carry changes that leave mTORC1 stuck "on", which is why this cancer responds to mTOR-blocking drugs at all. In one large trial, people with advanced kidney cancer lived longer on temsirolimus; in another, everolimus slowed the cancer's growth for a few months. Responding to the drug is not proof that mTORC1 started the cancer.Renal cancers frequently carry lesions that leave mTORC1 constitutively active, which is why this tissue responds to mTOR inhibitors. In two phase III trials in metastatic RCC, temsirolimus extended overall survival versus interferon alfa in poor-prognosis patients (HUD2007), and everolimus extended progression-free survival versus placebo after VEGF-targeted therapy (MOT2008). That the tumour responds to the drug is not the same as mTORC1 initiating the cancer. Holds under: Correlative, plus two randomised human trials showing the tumour responds to mTOR inhibitors: overall survival in poor-prognosis first-line RCC with temsirolimus (HUD2007), progression-free survival only after VEGF-targeted therapy with everolimus (MOT2008). This is response to treatment, not a demonstration that mTORC1 activation initiates RCC. The bladder-cancer responder case IYE2012 was removed from this edge on 2026-10-09 as a citation-population mismatch (it describes bladder, not kidney). shown in people · emerging, few independent studies	H	MOT2008, HUD2007
Temsirolimus inhibits Renal cell carcinoma (RCC) mechanism: clinical-outcome · this link in full · on the map table	In hard-to-treat kidney cancer, temsirolimus helped patients live longer compared with an older drug.In poor-prognosis renal cancer, temsirolimus improved overall survival against interferon - the hardest endpoint there is. Holds under: Poor-prognosis patients specifically; the combination arm did not beat temsirolimus alone. shown in people · settled in the literature	H	HUD2007

Evidence at a glance

Evidence	What it means	Studies
H	Human study	3
A	Animal model	2
R	Review — secondary literature, not a new result	1

Human studies in the Atlas

3 studies in people, newest first. Design and population as recorded for each study; the evidence code is the kind of study, not its quality.

Year	Evidence	Study	Design / population
2008	H	Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial MOT2008	Humans, phase III RCT (RECORD-1)
2007	H	Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma HUD2007	Humans, phase III RCT (n=626)
2004	H	Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma ATK2004	Humans: 111 patients with advanced refractory renal cell carcinoma, randomised to three weekly IV doses of temsirolimus (CCI-779)

Studies

Year	Evidence	Study
2008	H	Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial MOT2008 Everolimus extended median progression-free survival from 1.9 to 4.0 months versus placebo in metastatic renal cell carcinoma.
2007	H	Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma HUD2007 Temsirolimus alone extended median overall survival to 10.9 months versus 7.3 months with interferon alfa in poor-prognosis metastatic kidney cancer; rash, hyperglycemia, and hyperlipidemia were more common with temsirolimus.
2004	H	Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma ATK2004 In this randomised phase II trial, 111 patients with advanced renal cell carcinoma that had progressed on earlier therapy received temsirolimus (CCI-779) at 25, 75 or 250 mg as a weekly intravenous infusion. There was no control arm: randomisation compared dose levels only. The objective response rate was 7% (1 complete and 7 partial responses), with minor responses in a further 26%; median time to progression was 5.8 months and median survival 15.0 months. Neither efficacy nor toxicity differed significantly between the three doses, which supported taking the lowest dose (25 mg) forward. The commonest side effects were rash (76%), mouth sores (70%), weakness (50%) and nausea (43%); the commonest grade 3-4 events were high blood glucose (17%), low phosphate (13%), anaemia (9%) and high triglycerides (6%). Boundary: patients with advanced, previously treated kidney cancer; no placebo or active comparator, so survival figures cannot be attributed to the drug; risk-group analysis was retrospective.
2026	A	SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer TAN2026 Identifies a mechanism of mTOR-inhibitor (everolimus/temsirolimus) resistance in clear cell renal cell carcinoma: SPOP-driven K63-linked ubiquitination of ZMYND8 excludes it from phase-separation compartments, enabling a ZMYND8-ZHX2 complex that drives NEK7 transcription and alternative p70S6K activation independent of mTOR inhibition. A NEK7-targeting PROTAC restored everolimus sensitivity in ccRCC cells and mouse tumors, nominating NEK7 as a target to overcome mTOR-inhibitor resistance.
2013	A	Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma OKA2013 In mouse kidney tumours, active phosphorylated mTOR and total mTOR protein followed a 24-hour rhythm, set by the clock through the ubiquitin ligase Fbxw7. Giving everolimus when mTOR was high improved survival compared with other dosing times. Same drug, same dose - the clock time of dosing changed the outcome.
2007	R	Defining the role of mTOR in cancer GUE2007 Comprehensive review arguing mTOR signaling is commonly deregulated in human cancers, laying out the rationale for rapalog trials in oncology.

Related entities

mTOR 3 Everolimus 3 Temsirolimus 3 mTORC1 1 mTORC2 1 S6K1 1 Tumor growth 1

Cite this page

ShowHide

Barton, O. (2026). Renal cell carcinoma (RCC) [Entity page]. In Oliver's mTOR Atlas [Data set]. https://mtor-atlas.org/disease/renal-cell-carcinoma-rcc/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_disease_renal_cell_carcinoma_rcc,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}: Renal cell carcinoma (RCC)},
  howpublished = {Entity page in a data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/disease/renal-cell-carcinoma-rcc/},
  doi          = {10.5281/zenodo.22059963}
}

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