Gene

MTOR

mechanistic target of rapamycin kinase

Explore in graph →CI-GENE-00015849HGNC:3942 ENSG00000198793 NCBI 2475 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (32)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–32 of 32 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
MTOR A2034V2
MTOR Kinase Inhibitor AZD8055 + RapaLink-1Substitutes	Malignant Breast Neoplasm	Predictive	D	Does Not Support Resistance

Cohorts

Alteration frequency by cohort (181)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

gdcObserved181 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Kidney Chromophobe TCGA-KICH	Chromophobe Renal Cell Carcinoma

Literature

Linked publications (6)

25 per page, newest first.

pubmedPublishedShowing 1–6 of 6 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Analysis of mTOR Gene Aberrations in Melanoma Patients and Evaluation of Their Sensitivity to PI3K-AKT-mTOR Pathway Inhibitors.
· Clin Cancer Res · 2016 · PMID 26490311 · validated civic_curation pubmed
Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies.
· Cancer Res Commun · 2024 · PMID 38126764 · validated civic_curation pubmed
Response and acquired resistance to everolimus in anaplastic thyroid cancer.
· N Engl J Med · 2014 · PMID 25295501 · validated civic_curation pubmed
Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib.
· Cancer Discov · 2014 · PMID 24625776 ·

MTOR E1799K3
Everolimus	Focal Cortical DysplasiaUNRESOLVED	Predictive	D	Supports Sensitivity Response	4	submitted	EID9489 The L2427P (c.7280T>C) variant of mTOR was found in brain tissue samples from 2 focal cortical dysplasia type II (FCDII) patients at allelic frequencies of 9.6–12.6% and 6.9–7.3% in biological replica… (full text at CIViC) PMID 25799227 · Lim et al., 2015 · Open in CIViC	civic
〃	MegalencephalyUNRESOLVED	Predictive	D	Supports Sensitivity Response	3	submitted	EID9486 Three siblings had a phenotype which overlaps with known megalencephaly syndromes and RASopathies, including Costello syndrome, and were all heterozygous for mTOR c.5395G>A; p.Glu1799Lys. Peripheral b… (full text at CIViC) PMID 25851998 · Baynam et al., 2015 · Open in CIViC	civic
Sirolimus	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1321 Cell lines with various putative activating mutations were tested for sensitivity to rapamycin. The cell line SNU349, with MTOR mutation E1799K was hypersensitive to rapamycin treatment (IC50 of 0.19 … (full text at CIViC) PMID 24631838 · Grabiner et al., 2014 · Open in CIViC	civic

MTOR F2108L2
Everolimus	Thyroid Gland Anaplastic CarcinomaALIAS	Predictive	C	Supports Resistance	5	accepted	EID1110 After an 18-month sustained response to everolimus (in a patient with metastatic anaplastic thyroid carcinoma whose pretreatment tumor harbored a TSC2 Q1178* inactivating mutation, see EID1108), the r… (full text at CIViC) PMID 25295501 · Wagle et al., 2014 · Open in CIViC	civic
Sirolimus	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	4	accepted	EID1543 MCF-7 breast cancer cell line was exposed to mTOR inhibitors AZD8055 or rapamycin until resistance developed. Deep sequencing revealed an MTOR F2108L mutation in rapamycin-resistant clones (RR2 cells)… (full text at CIViC) PMID 27279227 · Rodrik-Outmezguine et al., 2016 · Open in CIViC	civic

MTOR H1968Y2
Capivasertib	Melanoma	Predictive	D	Supports Sensitivity Response	3	rejected	EID721 In a cell line with expression of H1968Y or P2213S mTOR mutations, LY294002 and AZD5363 were more effective than temsirolimus or BYL719 in suppressing cell growth. PMID 26490311 · Kong et al., 2016 · Open in CIViC	civic
Capivasertib + PI3K/BET Inhibitor LY294002Substitutes	Melanoma	Predictive	D	Supports Sensitivity Response	3	accepted	EID713 In a cell line (HEK293T) with expression of H1968Y or P2213S mTOR mutations, LY294002 and AZD5363 were more effective than temsirolimus or BYL719 in suppressing cell growth. PMID 26490311 · Kong et al., 2016 · Open in CIViC	civic

MTOR M2327I4
MTOR Kinase Inhibitor AZD8055	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	4	accepted	EID1544 MCF-7 breast cancer cell line was exposed to mTOR inhibitor AZD8055 until resistance developed. Deep sequencing revealed an MTOR M2327I mutation in the AZD8055-resistant clone. Downstream signalling w… (full text at CIViC) PMID 27279227 · Rodrik-Outmezguine et al., 2016 · Open in CIViC	civic
RapaLink-1 + SirolimusSubstitutes	Malignant Breast Neoplasm	Predictive	D	Does Not Support Resistance	3	accepted	EID1545 MCF-7 breast cancer cell line was exposed to mTOR inhibitor AZD8055 until resistance developed. Deep sequencing revealed an MTOR M2327I mutation in the AZD8055-resistant clone. These cells remained se… (full text at CIViC) PMID 27279227 · Rodrik-Outmezguine et al., 2016 · Open in CIViC	civic
Sirolimus	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	4	rejected	EID1546 MCF-7 breast cancer cell line was exposed to mTOR inhibitor rapamycin until resistance developed. Deep sequencing revealed an MTOR A2034V mutation in the resistant clone. Downstream signalling was ind… (full text at CIViC) PMID 27279227 · Rodrik-Outmezguine et al., 2016 · Open in CIViC	civic
RapaLink-1 + SirolimusSubstitutes	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	4	rejected	EID10082 MCF-7 breast cancer cell line was exposed to mTOR inhibitor AZD8055 until resistance developed. Deep sequencing revealed an MTOR M2327I mutation in the resistant clone (TKi-R). A novel mTOR inhibitor … (full text at CIViC) PMID 27279227 · Rodrik-Outmezguine et al., 2016 · Open in CIViC	civic

MTOR Mutation2
(prognostic)	Melanoma	Prognostic	B	Supports Poor Outcome	3	accepted	EID712 Median overall survival of patients with nonsynonymous mutations in mTOR was shorter. PMID 26490311 · Kong et al., 2016 · Open in CIViC	civic
Everolimus + PazopanibCombination	Bladder Carcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID705 A case-study of a patient with urothelial carcinoma reported exceptional response (14 months) in a phase 1 study of Everolimus and Pazopanib. Mutations E2014K and E2419K were shown to be activating in… (full text at CIViC) PMID 24625776 · Wagle et al., 2014 · Open in CIViC	civic

MTOR T1977K2
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	2	accepted	EID9479 Public cancer genome sequencing data sets were used to generated a catalog of mTOR pathway mutations, identified 33 MTOR mutations which confer pathway hyperactivation. A single instance of T1977K was… (full text at CIViC) PMID 24631838 · Grabiner et al., 2014 · Open in CIViC	civic
Sirolimus	Solid NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID7323 Sequencing data from 22 human kidney cancer cases was used to identify the activating mechanisms conferred by mTOR mutations. Cells that expressed activating mTOR mutants were sensitive to rapamycin t… (full text at CIViC) PMID 27482884 · Xu et al., 2016 · Open in CIViC	civic