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BIOMARKER:

MTOR mutation

i
Entrez ID:
Related biomarkers:
5d
Expression of mTOR, CD163, α-SMA, FOXp3 as survival predictors and its significance in patients with oral squamous cell carcinoma. (PubMed, BMC Oral Health)
The study reveals that over expression of CD163 and α-SMA is strongly associated with disease outcome. The combinations of all the four marker expression profile will be emerging strategy towards prognosis and also to determine survival outcomes in patients. This is a pioneering observation of these combinations of markers in OSCC despite certain limitations.
Retrospective data • Journal
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mTOR (Mechanistic target of rapamycin kinase) • CD163 (CD163 Molecule) • FOXP3 (Forkhead Box P3)
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MTOR mutation • CD163 overexpression • CD163 expression • FOXP3 expression
6d
Visualize PIM-1 Protein Function and Its Interaction With PI3K/Akt/mTOR Pathway Regulated by Its Active Sites Through FRET Biosensors. (PubMed, Biotechnol J)
Asp167 has few effects on both the catalytic function activity of PIM-1 and PI3K/AKT/mTOR pathway, even though the binding ability of PIM-1 protein to its substrate is dramatically inhibited by D167A mutation. Altogether, the mutant probes works well as visualization tools to unearth the function of active sites in PIM-1 kinase, not only facilitating the further clarification of molecular mechanism underlying PIM-1 related signaling pathways, but also shedding light on drug development and disease therapy targeting PIM-1 protein.
Journal
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PIM1 (Pim-1 Proto-Oncogene)
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MTOR mutation
8d
Development and Validation of the Predictive and Prognostic ChemoResist Signature in Resected Pancreatic Ductal Adenocarcinoma: Multicenter Study. (PubMed, Ann Surg)
The ChemoResist signature could precisely predict survival in PDAC undergoing resection and chemotherapy, and its predictive value surpassed TNM stage and other clinicopathologic factors. Moreover, the ChemoResist classifier could assist with identifying patients who would more likely benefit from adjuvant chemotherapy.
Clinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog)
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MTOR mutation
18d
Capivasertib: First Approved AKT inhibitor for the Treatment of Patients with Breast Cancer. (PubMed, Anticancer Agents Med Chem)
It is used for the treatment of adult patients with hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer with at least one alteration on PIK3CA/AKT1/PTEN. In this short perspective, Capivasertib's physicochemical properties, synthesis, mechanism of action, binding mode, pharmacokinetics, drug interaction studies, and treatment-emergent adverse events are discussed.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
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HR positive • HER-2 negative • EGFR positive • MTOR mutation
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Truqap (capivasertib)
20d
Advances in vascular anomalies: refining classification in the molecular era. (PubMed, Histopathology)
Moreover, the role of PIK3CA mutations in vascular overgrowth syndromes is explored, alongside emerging targeted therapies, such as PI3K and MEK inhibitors, that promise improved outcomes for patients with these challenging conditions. The integration of histology, molecular diagnostics, and multidisciplinary care remains critical for the accurate diagnosis and optimal treatment of vascular anomalies in the era of precision medicine.
Review • Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PIK3CA mutation • RAS mutation • MTOR mutation
1m
Genetic Validation of a TSC2 Immunohistochemistry Assay in TSC/mTOR-pathway Altered Renal Tumors. (PubMed, Hum Pathol)
Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in TSC2 showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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PIK3CA mutation • TSC1 mutation • TSC2 mutation • MTOR mutation
1m
Structure of the human TSC:WIPI3 lysosomal recruitment complex. (PubMed, Sci Adv)
Tuberous sclerosis complex (TSC) is targeted to the lysosomal membrane, where it hydrolyzes RAS homolog-mTORC1 binding (RHEB) from its GTP-bound to GDP-bound state, inhibiting mechanistic target of rapamycin complex 1 (mTORC1)...These structural advances provide a model by which WIPI3 and PIP-signaling networks coordinate to recruit TSC to the lysosomal membrane to inhibit mTORC1. The high-resolution TSC structure reveals previously unrecognized mutational hotspots and uncovers crucial insights into the mechanisms of TSC dysregulation in disease.
Journal
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TSC1 (TSC complex subunit 1) • RHEB (Ras Homolog, MTORC1 Binding)
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MTOR mutation
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sirolimus
1m
Metastatic renal cell carcinoma with fibromyomatous stroma associated with tuberous sclerosis or MTOR, TSC1/TSC2-Mutations: A Series of 4 cases and a review of the literature. (PubMed, Hum Pathol)
All patients were alive at last follow up (median follow-up of 85 months). Our report is intended to raise awareness regarding rare instances of metastatic behavior for M/TSC-RCCfms.
Review • Journal • Stroma • Metastases
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mTOR (Mechanistic target of rapamycin kinase) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • CA9 (Carbonic anhydrase 9) • KRT7 (Keratin-7)
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TSC1 mutation • TSC2 mutation • MTOR mutation
1m
The Bi-Steric Inhibitor RMC-5552 Reduces mTORC1 Signaling and Growth in Lymphangioleiomyomatosis. (PubMed, Am J Respir Cell Mol Biol)
Rapamycin inhibition of LAF growth was rapidly reversed, but RMC-5552 inhibition was more durable. RMC-5552, through its potential to eradicate LAM cancer SLS cells, may have therapeutic benefit in LAM and other diseases with mTORC1 hyperactivity.
Journal
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TSC1 (TSC complex subunit 1) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
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MTOR mutation
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RMC-5552
2ms
Genomic analysis of circulating tumor DNA (ctDNA) from patients with triple-negative, HER2-mutant metastatic breast cancer treated with neratinib as monotherapy or in combination with trastuzumab in the SUMMIT trial (SABCS 2024)
These findings were consistent with those reported for SUMMIT hormone receptor-positive (HR+) HER2-mutant mBC cohorts, in which patients treated with N or N + fulvestrant (N+F) experienced promising clinical responses but shorter DOR. Although limited by small numbers, addition of T to N in patients with HER2-mutant mTNBC, despite deepening and prolonging response, did not appear to preclude eventual emergence of either on-pathway (ERBB3) or off-pathway (KRAS, TP53) mutations. In contrast to observations in N+F+T-treated patients with HR+, HER2-mutant disease, no additional HER2 alterations were detected upon progression in N+T-treated patients with mTNBC in this small dataset. Future investigations may evaluate clinical utility of sequencing therapies targeted to mutations acquired in response to N-based therapy in patients with HER2-mutant mTNBC.
Clinical • Combination therapy • Genomic analysis • Circulating tumor DNA • Metastases • Omic analysis
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase)
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TP53 mutation • KRAS mutation • HR positive • HER-2 amplification • HER-2 mutation • KRAS Q61H • ERBB3 mutation • MTOR mutation • HER-2 T798I • TP53 R196*
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MSK-ACCESS
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Herceptin (trastuzumab) • Nerlynx (neratinib) • fulvestrant
2ms
Multigene Panel Next-Generation Sequencing Techniques in the Management of Patients with Metastatic Colorectal Carcinoma: The Way Forward for Personalized Treatment? A Single-Center Experience. (PubMed, Int J Mol Sci)
In total, 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited.
Journal • Next-generation sequencing • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • JAK1 (Janus Kinase 1)
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KRAS mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • FGFR2 mutation • KRAS G12 • ERBB3 mutation • MTOR mutation
2ms
Comparative targeted genome profiling between solid and liquid biopsies in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a proof-of-concept pilot study. (PubMed, Neuroendocrinology)
This pilot study explores the applicability of LB in GEP-NETs MP evaluation. Further studies with larger cohorts are needed to validate LB and to define the clinical impact.
Journal • Liquid biopsy • Tumor mutational burden • Biopsy
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TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • mTOR (Mechanistic target of rapamycin kinase) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MUTYH (MutY homolog) • DAXX (Death-domain associated protein) • DEPDC5 (DEP Domain Containing 5, GATOR1 Subcomplex Subunit) • MEN1 (Menin 1)
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PTEN mutation • ARID1A mutation • TSC2 mutation • MTOR mutation
2ms
Race- associated molecular differences in uterine serous carcinoma. (PubMed, Front Oncol)
Identifying actionable mutations in this high unmet need population is crucial to improving outcomes among Black patients with uterine malignancy. Development of new targeted-therapies will need to keep these alterations at the forefront as trials are being designed.
Journal
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CCNE1 (Cyclin E1)
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CCNE1 amplification • MTOR mutation
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FoundationOne® CDx
2ms
Hepatoid thymic carcinoma in a polycythemia vera patient treated with ropeginterferon Alfa-2b: Clinical, histopathological and molecular correlates. (PubMed, Pathol Res Pract)
Whole exome sequencing revealed loss of function mutations in TP53, STK11, PBRM1, SMAD3, FN1, NTRK1, and FANCD2, as well as gain of function mutations in MTOR, BCL11A and COL1A1, along with amplification of CCND3 and MDM2. This mutational landscape halfway between thymic carcinoma (TP53, PBRM1) and hepatoid variant carcinoma of other sites (STK11) suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.
Journal
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TP53 (Tumor protein P53) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • STK11 (Serine/threonine kinase 11) • mTOR (Mechanistic target of rapamycin kinase) • MDM2 (E3 ubiquitin protein ligase) • PBRM1 (Polybromo 1) • CCND3 (Cyclin D3) • COL1A1 (Collagen Type I Alpha 1 Chain) • FANCD2 (FA Complementation Group D2) • BCL11A (BAF Chromatin Remodeling Complex Subunit BCL11A) • SLC2A1 (Solute Carrier Family 2 Member 1) • SMAD3 (SMAD Family Member 3)
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TP53 mutation • STK11 mutation • PBRM1 mutation • MTOR mutation • MDM2 mutation
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Besremi (ropeginterferon alfa-2b-njft)
3ms
The PIK3CA gene and its pivotal role in tumor tropism of triple-negative breast cancer. (PubMed, Transl Oncol)
A detailed exploration of PIK3CA-targeted strategies in the therapeutic arena is presented, outlining the current landscape of clinical trials and precision medicine approaches. As the scientific narrative converges, this review underscores the critical role of PIK3CA in shaping the molecular intricacies of TNBC tumor tropism and illuminates pathways toward tailored interventions, promising a paradigm shift in the clinical management of TNBC.
Review • Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PIK3CA mutation • MTOR mutation
3ms
Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort. (PubMed, Br J Cancer)
Phosphoprotein-based measurements of drug targets and downstream substrates should be captured along with genomic information to identify MBCs driven by the PI3K/AKT/mTOR signalling.
Journal • Real-world evidence • Real-world • Metastases
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PIK3CA mutation • MTOR mutation
3ms
Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer (clinicaltrials.gov)
P2, N=74, Completed, GOG Foundation | Active, not recruiting --> Completed
Trial completion • Trial completion date • Metastases
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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KRAS mutation • PIK3CA mutation • MTOR mutation
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everolimus • tamoxifen • letrozole
3ms
Genomic alterations associated with high Tumor Mutation Burden (TMB-H) status in advanced solid tumors: A single tertiary care oncology center experience from India (ESMO Asia 2024)
TMB-H tumors had a significant enrichment for alterations in genes encoding proteins involved in the DNA repair pathway and growth factor receptor signal transduction. Combining immune checkpoint inhibitors with targeted therapies aimed at specific pathways could be further explored to potentially enhance outcomes for patients with solid tumors.
Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • IO biomarker • Metastases
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • mTOR (Mechanistic target of rapamycin kinase) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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BRCA1 mutation • TMB-H • MSI-H/dMMR • TMB-L • APC mutation • MTOR mutation
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Guardant360® CDx • Guardant360 TissueNext™
3ms
Macroautophagy/autophagy promotes resistance to KRASG12D-targeted therapy through glutathione synthesis. (PubMed, Cancer Lett)
Consequently, genetic interventions (utilizing ATG5 or BECN1 knockout) or pharmacological inhibition of autophagy (with chloroquine, bafilomycin A1, or spautin-1) enhance the anticancer activity of MRTX1133 in vitro and in various animal models (subcutaneous, patient-derived xenograft, and orthotopic). Moreover, the release of histones by apoptotic cells triggers an adaptive immune response when combining an autophagy inhibitor with MRTX1133 in immunocompetent mice. These findings establish a new strategy to overcome KRASG12D-targeted therapy resistance by inhibiting autophagy-dependent glutathione synthesis.
Journal
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KRAS (KRAS proto-oncogene GTPase) • ATG5 (Autophagy Related 5) • APAF1 (Apoptotic peptidase activating factor 1) • BECN1 (Beclin 1)
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KRAS mutation • KRAS G12D • KRAS G12 • MTOR mutation
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MRTX1133 • chloroquine phosphate
3ms
Multifocal, multiphenotypic tumours arising from an MTOR mutation acquired in early embryogenesis. (PubMed, Oncogene)
Biochemical and structural analysis of their shared MTOR mutation, absent from normal tissues, demonstrates enhanced protein flexibility, enabling a FAT domain hinge to dramatically increase activity of mTORC1 and mTORC2. Developmental mutations, not usually detected in traditional genetic screening, have vital clinical importance in guiding prognosis, targeted treatment, and family screening decisions for paediatric tumours.
Journal
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mTOR (Mechanistic target of rapamycin kinase)
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MTOR mutation
4ms
A Scoping Review of Population Diversity in the Common Genomic Aberrations of Clear Cell Renal Cell Carcinoma. (PubMed, Oncology)
Studying the genetic aberrations that frequently occur in different regions gives insight into what current research lacks. When more genomic landscape research arises, precision therapy, risk calculators, and artificial intelligence may help better prognosticate and individualize treatment for those at risk for ccRCC. Provided the scarcity of existing data, and the rising prevalence of ccRCC, more studies must be conducted at the clinical level.
Review • Journal
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mTOR (Mechanistic target of rapamycin kinase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)
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PBRM1 mutation • MTOR mutation
4ms
Renal eosinophilic vacuolated tumor: a clinicopathological analysis of seven cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
The use of combined immunohistochemical stains greatly aids in its diagnosis. Typically, the tumor exhibits indolent biological behaviors with a favorable prognosis.
Journal
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KIT (KIT proto-oncogene, receptor tyrosine kinase) • CCND1 (Cyclin D1) • VIM (Vimentin) • MME (Membrane Metalloendopeptidase) • CTSK (Cathepsin K) • CLDN7 (Claudin 7)
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MTOR mutation • CCND1 expression
7ms
Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG (clinicaltrials.gov)
P1, N=12, Recruiting, Nader Sanai | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2025
Trial completion date • Trial primary completion date
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • mTOR (Mechanistic target of rapamycin kinase) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta)
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PIK3CA mutation • MTOR mutation • PIK3CA mutation + PTEN mutation • PIK3R1 mutation
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Torisel (temsirolimus)
7ms
Mechanism of targeting the mTOR pathway to regulate ferroptosis in NSCLC with different EGFR mutations. (PubMed, Oncol Lett)
The results showed that, compared with EGFR wild-type/sensitive mutant cells, EGFR-resistant mutant cells were more sensitive to the ferroptosis inducer, erastin. In the present study, GPX4 inhibitor only or combined with RAD001 inhibited the AKT/mTOR pathway in EGFR-resistant mutant cells. Therefore, the results of the present study suggested that inhibition of the mTOR pathway may downregulate the expression of ferroptosis-related proteins in EGFR-resistant and EGFR wild-type NSCLC cells, increase the ROS and MDA levels and ultimately induce ferroptosis.
Journal
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EGFR (Epidermal growth factor receptor) • GPX4 (Glutathione Peroxidase 4)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR wild-type • EGFR L858R + EGFR T790M • MTOR mutation • EGFR H1975
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everolimus • erastin
8ms
Plasmacytoid Urothelial Carcinoma of the Urinary Bladder - a Clinicopathological and Molecular Analysis of 52 Cases. (PubMed, Hum Pathol)
Plasmacytoid UC is an aggressive histologic subtype that demonstrates frequent somatic gene mutations and CNVs, which may underlie its oncogenesis and progression. Gene mutations of the mTOR pathway are associated with poor outcome in a subset of patients with plasmacytoid UC.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TERT (Telomerase Reverse Transcriptase) • CDH1 (Cadherin 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • HER-2 overexpression • MTOR mutation • PIK3R1 mutation
8ms
Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer. (PubMed, Cancer Immunol Immunother)
In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.
Journal • IO biomarker
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • mTOR (Mechanistic target of rapamycin kinase)
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EGFR mutation • BRAF mutation • MTOR mutation
8ms
MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level. (PubMed, Cancer Biol Ther)
Additionally, significant differences were observed in the genomic landscapes between the subtypes: MOICS1 exhibited mutations in TTN, BAP1, SETD2, MTOR, MUC16, CSMD3, and AKAP9, while MOICS2 was characterized by notable alterations in the TGF-β pathway. Overall, our work demonstrates that multi-immune omics remodeling analysis enhances the understanding of the immune heterogeneity in ccRCC and supports precise patient management.
Journal
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CD8 (cluster of differentiation 8) • mTOR (Mechanistic target of rapamycin kinase) • BAP1 (BRCA1 Associated Protein 1) • MUC16 (Mucin 16, Cell Surface Associated) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD4 (CD4 Molecule) • TGFB1 (Transforming Growth Factor Beta 1) • CSMD3 (CUB And Sushi Multiple Domains 3)
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BAP1 mutation • MTOR mutation • TTN mutation • SETD2 mutation
8ms
Molecular characterization and survival analysis of a cohort of glioblastoma, IDH-wildtype. (PubMed, Pathol Res Pract)
Multivariate analysis to account for the effect of MGMT promoter methylation and age showed that, in contrast to other published series, this cohort demonstrated improved survival for tumors harboring PTEN mutations, and that there was no observed difference for most other molecular alterations, including EGFR amplification, RB1 loss, or the coexistence of EGFR amplification and deletion/exon skipping (EGFRvIII). Despite limitations in sample size, this study contributes data to the molecular landscape of glioblastomas, prompting further investigations to examine these findings more closely in larger cohorts.
Journal
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EGFR (Epidermal growth factor receptor) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • mTOR (Mechanistic target of rapamycin kinase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • MDM4 (The mouse double minute 4) • PI3K (Phosphoinositide 3-kinases)
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TP53 mutation • EGFR amplification • PTEN mutation • MGMT promoter methylation • MTOR mutation • TERT mutation • IDH wild-type • TERT promoter mutation
9ms
The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer is driven by molecular features. (PubMed, J Pathol Clin Res)
Overall survival was longer in patients with pS6 ≥ 3rd quartile (27.6 versus 19.3 months, p = 0.038) and in patients with any mutation in the PIK3CA/AKT/mTOR pathway (27.6 versus 19.3 months, p = 0.011). The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer appears primarily driven by molecular features associated with the activation of the PIK3CA/AKT/mTOR pathway.
Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
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ER positive • HER-2 negative • PIK3CA mutation • PTEN expression • AKT1 mutation • MTOR mutation
|
everolimus
9ms
Spatial omics reveals molecular changes in focal cortical dysplasia type II. (PubMed, Neurobiol Dis)
Our comparative analysis of protein pathways and enriched Gene Ontology pathways related to myelination in the FCD type II-affected mouse model and human FCD type IIb transcriptomics highlights the animal model's translational value. This dual approach, including mouse model proteomics and human transcriptomics strengthens our understanding of the functional consequences arising from somatic mutations in FCD type II, as well as the identification of pathways that may be used as therapeutic strategies in the future.
Journal
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mTOR (Mechanistic target of rapamycin kinase) • RHEB (Ras Homolog, MTORC1 Binding)
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MTOR mutation
9ms
Recurrent Tuberous Sclerosis Complex​​​​​/Mammalian Target of Rapamycin Mutations Define Primary Renal Hemangioblastoma as a Unique Entity Distinct From Its Central Nervous System Counterpart. (PubMed, Am J Surg Pathol)
This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification.
Journal
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mTOR (Mechanistic target of rapamycin kinase) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • GPNMB (Glycoprotein Nmb)
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TSC1 mutation • TSC2 mutation • MTOR mutation
10ms
L1CAM Expression and Molecular Alterations Distinguish Low Grade Oncocytic Tumor (LOT) from Eosinophilic Chromophobe Renal Cell Carcinoma. (PubMed, Mod Pathol)
Our study further supports LOT as a unique entity with benign clinical course. Based on the likely cell of origin and its clinicopathologic characteristics, we propose that changing the nomenclature of LOT to "Oncocytic Principal Cell Adenoma of the Kidney" may be a better way to define and describe this entity.
Journal
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L1CAM (L1 cell adhesion molecule) • RHEB (Ras Homolog, MTORC1 Binding)
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MTOR mutation
10ms
Genetic ancestry associations with prostate adenocarcinoma mutational profiles: New Insights from a diverse 5,959-patient real-world cohort (AACR 2024)
Lastly, we identified novel positive associations between AMR and driver mutations in PIK3C3A (OR=1.12, p=0.0003) as well as small NS mutations or CNAs in the PI3K/AKT/mTOR pathway genes (OR=1.03, p=0.04). By analyzing a large, diverse real-world cohort and leveraging NGS-inferred genetic ancestry, our study confirms known associations between somatic alterations in PRAD cancer genes and race and ethnicity, while unveiling novel associations in understudied populations of potential significance for understanding disparities in disease outcomes.
Real-world evidence • Clinical • Real-world
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ERG (ETS Transcription Factor ERG) • SPOP (Speckle Type BTB/POZ Protein) • FOXA1 (Forkhead Box A1) • TMPRSS2 (Transmembrane serine protease 2) • PIK3C3 (Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3)
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TP53 mutation • PIK3CA mutation • PTEN mutation • MTOR mutation • SPOP mutation • TMPRSS2-ERG fusion • FOXA1 mutation
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Tempus xT Assay
10ms
Novel molecular subtypes of intracranial germ cell tumours expand therapeutic opportunities. (PubMed, Neuro Oncol)
Novel genomic aberrations and molecular subtypes were identified in IGCTs. These findings provide molecular basis for the potential introduction of new treatment strategies in this setting.
Journal
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KRAS (KRAS proto-oncogene GTPase) • CRKL (CRK Like Proto-Oncogene, Adaptor Protein)
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KRAS mutation • KRAS amplification • MTOR mutation • CRKL amplification
10ms
A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours (clinicaltrials.gov)
P2, N=137, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Jan 2024 --> Dec 2024
Trial completion date • Metastases
|
PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1)
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EGFR mutation • PTEN mutation • NF1 mutation • MTOR mutation • AKT1 amplification
|
sunitinib • Torisel (temsirolimus)
10ms
Disruption of Autophagic Flux and Treatment with the PDPK1 Inhibitor GSK2334470 Synergistically Inhibit Renal Cell Carcinoma Pathogenesis. (PubMed, J Cancer)
Importantly, GSK470 and chloroquine synergistically inhibited the growth of RCC cells in vitro and in xenograft models, supporting the protective role of autophagy activation upon blockade of the PDPK1-Akt-mTOR signaling pathway. Our study provides new insight into PDPK1 inhibition combined with autophagy inhibition as a useful treatment strategy for RCC.
Journal
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IGF1 (Insulin-like growth factor 1) • PDPK1 (3-Phosphoinositide dependent protein kinase 1)
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MTOR mutation
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GSK2334470
11ms
Recurrent MTOR Mutations in Renal Cell Carcinoma With Fibromyomatous Stroma: A Report of 2 Tumors. (PubMed, Int J Surg Pathol)
Recent evidence suggests recurrent alterations in the mTOR pathway, supporting its recognition as a distinct entity. Herein, we report 2 renal cell carcinomas with fibromyomatous stroma with MTOR mutations occurring in 62- and 72-year-old women and review the literature to support its recognition as a distinct entity, focusing on the characteristic morphology, immunohistochemical staining patterns as well as genetic alterations.
Journal • Stroma
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mTOR (Mechanistic target of rapamycin kinase)
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MTOR mutation
11ms
Genetic alterations in thyroid cancer mediating both resistance to BRAF inhibition and anaplastic transformation. (PubMed, Oncotarget)
Transition to an immune-suppressed state is another correlate of BRAF inhibitor resistance and tumor dedifferentiation, suggesting a possible role for concurrent targeted therapy with immunotherapy. Investigations into combined targeted and immunotherapy are ongoing, but early results with checkpoint inhibitors, viral therapies, and CAR T-cells suggest enhanced anti-tumor immune activity with these combinations.
Journal • IO biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • mTOR (Mechanistic target of rapamycin kinase) • PBRM1 (Polybromo 1) • NF2 (Neurofibromin 2) • JAK1 (Janus Kinase 1) • ARID2 (AT-Rich Interaction Domain 2) • PI3K (Phosphoinositide 3-kinases) • RASA1 (RAS P21 Protein Activator 1)
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BRAF V600E • PIK3CA mutation • BRAF V600 • PBRM1 mutation • MTOR mutation
11ms
A NOVEL MTORC2-AKT-ROS AXIS TRIGGERS MITOFISSION and MITOPHAGY-ASSOCIATED EXECUTION of COLORECTAL CANCER CELLS UPON DRUG-INDUCED ACTIVATION of MUTANT KRAS. (PubMed, Autophagy)
Importantly, we identified MTOR (mechanistic target of rapamycin kinsase) complex 2 (MTORC2) as the upstream mediator of AKT phosphorylation at S473 in our model...Finally, increase in thermal stability of KRAS, AKT and DNM1L were observed upon exposure to C1 only in mutant KRAS-expressing cells. Taken together, our work has unraveled a novel mechanism of selective targeting of mutant KRAS-expressing cancers via MTORC2-mediated AKT activation and ROS-dependent mitofission, which could have potential therapeutic implications given the relative lack of direct RAS-targeting strategies in cancer.
Journal
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KRAS (KRAS proto-oncogene GTPase) • VDAC1 (Voltage Dependent Anion Channel 1)
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KRAS mutation • MTOR mutation
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sirolimus
12ms
Diagnostic utility of genetic alterations in distinguishing IDH-wildtype glioblastoma from lower-grade gliomas: Insight from next-generation sequencing analysis of 479 cases. (PubMed, Brain Pathol)
Some molecular alterations enriched in GBM offer valuable insights for molecular diagnosis and glioma classification. Furthermore, high-grade diffuse astrocytic gliomas featuring mTOR pathway mutations in the absence of molecular diagnostic features of GBM could represent more favorable tumor types distinct from GBM.
Journal • Next-generation sequencing • Tumor mutational burden
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EGFR (Epidermal growth factor receptor) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog)
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EGFR mutation • TMB-H • PTEN mutation • MTOR mutation • IDH wild-type
12ms
Genomic and Immunophenotypic Landscape of Acquired Resistance to PD-(L)1 Blockade in Non-Small-Cell Lung Cancer. (PubMed, J Clin Oncol)
These findings highlight the genomic and immunophenotypic heterogeneity of ICI resistance in NSCLC, which will need to be considered when developing novel therapeutic strategies aimed at overcoming resistance.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • STK11 (Serine/threonine kinase 11) • JAK2 (Janus kinase 2) • KEAP1 (Kelch Like ECH Associated Protein 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • mTOR (Mechanistic target of rapamycin kinase) • B2M (Beta-2-microglobulin) • JAK1 (Janus Kinase 1) • CD3E (CD3 Epsilon Subunit Of T-Cell Receptor Complex)
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STK11 mutation • MTOR mutation
12ms
Elevated FBXL6 activates both wild-type KRAS and mutant KRAS and drives HCC tumorigenesis via the ERK/mTOR/PRELID2/ROS axis in mice. (PubMed, Mil Med Res)
FBXL6 activates KRAS or KRAS via ubiquitination at the site K128, leading to activation of the ERK/mTOR/PRELID2/ROS axis and tumorigenesis. Dual inhibition of MEK and mTOR effectively protects against FBXL6- and KRAS-induced tumorigenesis, providing a potential therapeutic strategy to treat this aggressive subtype of liver cancer.
Preclinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • mTOR (Mechanistic target of rapamycin kinase)
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KRAS mutation • KRAS wild-type • RAS wild-type • MTOR mutation