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    DRUG CLASS:

    mTOR inhibitor

    Related drugs:
    5d
    Enhancement of apoptosis in HCT116 and HepG2 cells by Coix lacryma-jobi var. lacryma-jobi seed extract in combination with sorafenib. (PubMed, Chin Herb Med)
    Additionally, the combination treatment's effect on the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway was investigated. The combination of CLCD with sorafenib demonstrates significant potential as a strategy for future anticancer therapies. This CL seed extract, cultivated and commercially available in Thailand, shows promise as a natural supplement to enhance the efficacy of chemotherapy in upcoming clinical anticancer applications.
    Journal
    |
    CAT (Catalase) • SOD2 (Superoxide Dismutase 2)
    |
    sorafenib • sirolimus
    5d
    Acacetin as a natural cardiovascular therapeutic: mechanisms and preclinical evidence. (PubMed, Front Pharmacol)
    Meanwhile, several critical signaling pathways have also been found to mediate the protection of acacetin against CVDs, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR), sirtuin 1/AMP-activated protein kinase/peroxisome proliferator-activated receptor-γ coactivator-1α (Sirt1/AMPK/PGC-1α), transforming growth factor-β1/small mothers against decapentaplegic 3 (TGF-β1/Smad3), protein kinase B/endothelial nitric oxide synthase (Akt/eNOS), and others. Finally, we highlight the existing problems associated with acacetin that need to be addressed, such as the requirement for clinical evidence and enhanced bioavailability, as well as its potential as a promising cardiovascular drug candidate.
    Preclinical • Review • Journal
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    mTOR (Mechanistic target of rapamycin kinase) • SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1) • NOS3 (Nitric oxide synthase 3) • SIRT1 (Sirtuin 1) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1) • SMAD3 (SMAD Family Member 3)
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    sirolimus
    6d
    Structural and Energetic Insights into the Binding of L- and D-Arginine Analogs with Neuropilin-1 (NRP1): Molecular Docking, Molecular Dynamics and DFT Calculations. (PubMed, Cell Biochem Biophys)
    Since arginine (Arg) regulates nutrient-responsive rapamycin signaling, which in turn regulates cell growth and metabolism, Arg, as well as simple structural variations of L- and D-Arg, were selected to study in-silico structural and energetic influences of such ligands on NRP1 signaling...Structural and energetic analyses were performed to examine further L-/D-Agd and L-/D-Agn. Quantum mechanical calculations were performed to confirm the outcomes obtained from docking computations and MD simulations.
    Journal
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    NRP1 (Neuropilin 1)
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    sirolimus
    8d
    CEP55, A Promising Prognostic Biomarker for Pancreatic Neuroendocrine Neoplasms, Promotes Tumor Progression Through Activation of PI3K/AKT/mTOR Pathway. (PubMed, FASEB J)
    Everolimus, an mTOR inhibitor, was shown to counteract the effects of CEP55 overexpression both in vivo and in vitro. In conclusion, CEP55 may enhance the proliferation, invasion, and migration of pNENs by activating the PI3K/AKT/mTOR pathway through its interaction with PI3K. It may serve as a valuable prognostic marker and a promising therapeutic target.
    Journal
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    BIRC2 (Baculoviral IAP Repeat Containing 2) • CEP55 (Centrosomal Protein 55)
    |
    everolimus
    9d
    GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases (clinicaltrials.gov)
    P1, N=21, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    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) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • INPP5D (Inositol Polyphosphate-5-Phosphatase D) • PIK3C3 (Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3) • PIK3R2 (Phosphoinositide-3-Kinase Regulatory Subunit 2 ) • PIK3R3 (Phosphoinositide-3-Kinase Regulatory Subunit 3)
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    paxalisib (GDC-0084)
    9d
    Multi-omics Analysis of Histone-related Genes in Osteosarcoma: A Multidimensional Integrated Study Revealing Drug Sensitivity and Immune Microenvironment Characteristics. (PubMed, Technol Cancer Res Treat)
    Drug sensitivity analysis revealed that the low-risk group was more sensitive to Imatinib, Rapamycin, and Sunitinib, while the high-risk group was more sensitive to MAPK pathway inhibitors.ConclusionThis study systematically revealed the spatial heterogeneity of histone modifications in OS and their clinical significance for the first time, proposing an "epigenetic-immune" regulatory network hypothesis and developing a histone modification-based prognostic model. Our proposed "epigenetic-guided personalized medication strategy" provides new insights for precision treatment of OS, potentially significantly improving patient prognosis.
    Journal
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    CD8 (cluster of differentiation 8) • SPP1 (Secreted Phosphoprotein 1)
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    imatinib • sunitinib • sirolimus
    9d
    Differential benefit of adjuvant everolimus according to endocrine therapy backbone in the randomized UNIRAD trial. (PubMed, ESMO Open)
    The present post hoc analyses generate hypotheses regarding the interaction between menopausal status, tamoxifen, and everolimus in patients with high-risk, ER-positive, human epidermal growth factor receptor type 2-negative early breast cancer. They suggest that tamoxifen alone is an underpowered endocrine treatment in high-risk premenopausal patients.
    Clinical • Journal
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    ER positive • PGR positive • EGFR positive
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    everolimus • tamoxifen
    10d
    Leveraging Technology to Improve Medication Adherence in Youth With Kidney or Liver Transplant (clinicaltrials.gov)
    P=N/A, N=65, Recruiting, Johns Hopkins University | Trial completion date: Jun 2026 --> Nov 2026 | Trial primary completion date: Mar 2026 --> Sep 2026
    Trial completion date • Trial primary completion date
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    sirolimus
    10d
    Sirolimus for Injection (Albumin-bound) Combined With Fulvestrant for HR+/HER2- Advanced/Metastatic Breast Cancer Patients Previously Treated With CDK4/6 Inhibitors (clinicaltrials.gov)
    P3, N=312, Not yet recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
    New P3 trial
    |
    fulvestrant • sirolimus • sirolimus for injection (albumin-bound) (SRL-HSA)
    11d
    KRASG12C/mTORC1 inhibition: a powerful duo in NSCLC therapeutics. (PubMed, Trends Pharmacol Sci)
    designed a combinational treatment based on targeting the active-state KRASG12C-mutant variant that characterizes a substantial subset of non-small-cell lung cancer (NSCLC) cases. The authors highlighted that dual targeting with KRASG12C (ON) and mammalian target of rapamycin (mTOR) complex (mTORC)-1-selective inhibition potentially provides a new strategy to overcome drug resistance.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • mTOR (Mechanistic target of rapamycin kinase)
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    KRAS mutation • KRAS G12C • KRAS G12
    11d
    Comprehensive analysis of glycometabolism-related genes reveals PLOD2 as a prognostic biomarker and therapeutic target in gastric cancer. (PubMed, BMC Gastroenterol)
    This study identifies PLOD2 as a key prognostic biomarker and therapeutic target in gastric cancer. As a central component in a glycometabolism-related model, PLOD2 promotes glycolysis, tumor progression, and immune evasion via the PI3K/AKT/mTOR pathway. The model effectively stratifies patient risk, offering both prognostic utility and therapeutic insight. Targeting PLOD2-mediated pathways may represent a promising strategy for precision therapy and improved clinical outcomes in gastric cancer.
    Journal
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    PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) • SLC5A1 (Solute Carrier Family 5 Member 1)
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    sirolimus
    12d
    POLR1D, a shared subunit of RNA polymerase I and III, modulates mTORC1 activity. (PubMed, Biochim Biophys Acta Mol Cell Res)
    The mechanistic target of rapamycin complex 1 (mTORC1) is a crucial nutrient sensor and a major regulator of cell growth and proliferation...We have identified a novel role for the RNA polymerase I/III subunit POLR1D in regulating mTORC1 signalling. Our findings suggest the existence of a new node in the already complex mTORC1 signalling network, where POLR1D functions to convey the cell's internal status, namely polymerase assembly, to this kinase.
    Journal
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    POLR1D (RNA Polymerase I And III Subunit D)
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    sirolimus
    13d
    Evaluation of circulating cytokine concentrations and ex vivo indicators of the inflammatory response in transition dairy cows fed pre- and postpartum diets differing in metabolizable protein supply. (PubMed, J Dairy Sci)
    The nutrient deficit during the transition period might alter activity of the nutrient sensing mechanistic target of rapamycin, thereby influencing immune phenotype and the inflammatory balance of transition cows...In summary, while serum IL-10 and IFN-γ concentrations were greatest during late gestation, whole blood LPS-induced cytokines and phagocytosis increased to a greater extent during early lactation suggesting a robust inflammatory response. However, increasing the MP supply during the transition period did not meaningfully influence indicators of the inflammatory response.
    Preclinical • Journal
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    mTOR (Mechanistic target of rapamycin kinase) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10)
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    sirolimus
    13d
    Valproic acid promotes transcriptional activation of Drd2 by mediating histone acetylation to inhibit the mTOR-Pttg1 signaling axis and exerts anti-PitNETs activity. (PubMed, Phytomedicine)
    Our results revealed that VPA exerts anti-PitNET effects by promoting Drd2 transcriptional activation, thereby inhibiting the mTOR-Pttg1 signaling axis, indicating the potential therapeutic utility of VPA in PitNET treatment.
    Journal
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    PTTG1 (PTTG1 Regulator Of Sister Chromatid Separation, Securin) • DRD2 (Dopamine Receptor D2) • PRL (Prolactin)
    |
    sirolimus
    15d
    Lymphangioleiomyomatosis: Update on Pathophysiology, Diagnosis, and Treatment (PubMed, Rev Med Chil)
    Sirolimus, an mTOR inhibitor, is the first-line therapy and has shown to stabilize lung function and reduce symptoms. In advanced cases, lung transplantation is a viable option. Hormone therapy and some surgical procedures are currently not recommended due to inconsistent results.
    Review • Journal
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    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • VEGFD (Vascular Endothelial Growth Factor D)
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    sirolimus
    15d
    Oncogenic β-catenin stimulation of cofilin 1-mediated macropinocytosis is druggable for cancer. (PubMed, Theranostics)
    Moreover, both excessive macropinocytosis induced by OSI-027 and macropinocytosis inhibition via CFL1 depletion suppressed β-catenin-driven tumor growth in orthotopic hepatocellular carcinoma model mice. Targeting macropinocytosis represents a promising therapeutic strategy for β-catenin mutant cancers.
    Journal
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    CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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    AVTX-006
    15d
    A Gain-of-Function Mutation in Mechanistic Target of Rapamycin Results in a Tuberous Sclerosis Complex-Like Manifestation of Parenchymal Lung Disease. (PubMed, Chest)
    Next-generation DNA sequencing of the tissue showed a previously described gain-of-function mutation in MTOR. We propose that this patient's TSC-like pulmonary disease is a direct result of this mutation, a novel finding that underscores the role of Next-generation DNA sequencing in cryptic histopathology.
    Journal
    |
    mTOR (Mechanistic target of rapamycin kinase) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
    |
    sirolimus
    16d
    Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer (clinicaltrials.gov)
    P3, N=236, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026
    Trial completion date
    |
    AFP (Alpha-fetoprotein)
    |
    AFP elevation
    |
    cisplatin • doxorubicin hydrochloride • irinotecan • Torisel (temsirolimus) • vincristine • fluorouracil topical • dexrazoxane
    18d
    Pulsed Radiofrequency Alleviates Acute Soft Tissue Injury in Rats by Regulating the TNF/mTOR Signaling Pathway. (PubMed, Photobiomodul Photomed Laser Surg)
    Further, we evaluated the gene expression of Ccl1, interleukin-6 (IL-6), nuclear factor-kappa-B-inhibitor alpha (Nfkbia), Akt1, Jun, Fos, and Caps3 in the model and PR-treated groups, all of which are key genes in the tumor necrosis factor (TNF)/mechanistic target of rapamycin (mTOR) signaling pathway according to the KEGG analysis...These data indicate that PR alleviated ASTI in rats by mediating redox homeostasis and the inflammatory response, which might be modulated by the TNF/mTOR signaling pathway. Thus, this study contributes to the understanding of ASTI progression and provides more substantial information about the genetic mechanism underlying the therapeutic effects of PR on ASTI.
    Preclinical • Journal
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    AKT1 (V-akt murine thymoma viral oncogene homolog 1) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL1B (Interleukin 1, beta) • NFKBIA (NFKB Inhibitor Alpha 2)
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    sirolimus
    18d
    Alkaline Phosphatase and ATG4B Sequentially Activated Fluorescent Probe for Cancer Cell-Specific Live Imaging of Autophagy. (PubMed, Anal Chem)
    Notably, the bright fluorescence of NBD was observed in cancer cells MDA-MB-231 and HeLa, while normal cells NIH3T3 exhibited weaker fluorescence, allowing differentiation between cancer and normal cells using a rapamycin (Rap)-induced autophagy cell model...Finally, animal experiments revealed that NBD-1p-Dabcyl effectively facilitated in situ fluorescence imaging of autophagy in tumor tissues. The design of this sequentially activated peptide probe offers a practical approach for monitoring autophagy in cancer cells, enabling high-throughput screening of autophagy inhibitors for cancer therapy.
    Journal
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    ATG4B (Autophagy Related 4B Cysteine Peptidase)
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    sirolimus
    19d
    Thin Versus Thicker Strut Thickness Stents in Primary Percutaneous Intervention (clinicaltrials.gov)
    P=N/A, N=146, Completed, Assiut University
    New trial
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    sirolimus
    20d
    Activating autophagy to eliminate toxic protein aggregates with small molecules in neurodegenerative diseases. (PubMed, Pharmacol Rev)
    Moreover, we underscore the activation of autophagy as a potential therapeutic strategy across different NDs and small molecules capable of activating autophagy pathways, such as rapamycin targeting the mTOR pathway to clear α-synuclein and Sertraline targeting the AMPK/mTOR/RPS6KB1 pathway to clear Tau, to further illustrate their potential in NDs' therapeutic intervention. It also elucidates the fascinating interrelationships between toxic proteins and the process of autophagy of "chasing and escaping" phenomenon. Moreover, the review further discusses the progress utilizing small molecules to activate autophagy to improve the efficacy of therapies for neurodegenerative diseases by removing toxic protein aggregates.
    Review • Journal
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    TARDBP (TAR DNA Binding Protein) • RPS6KB1 (Ribosomal Protein S6 Kinase B1)
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    sirolimus
    21d
    A Randomized clinical trial evaluating the impact on survival and quality of life of 177Lutetium[Lu]-edotreotide versus everolimus in patients with neuroendocrine tumors of the lung and thymus: the LEVEL study (GETNE T-2217). (PubMed, BMC Cancer)
    The LEVEL trial will investigate if 177Lu-edotreotide has the potential to be incorporated as a standard treatment option for patients with NETs from the lung and Thymus.
    Clinical • Clinical protocol • Journal • HEOR
    |
    SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2)
    |
    everolimus • Solucin (177Lu-edotreotide)
    22d
    FANTOM II: Safety & Performance Study of the FANTOM Sirolimus-Eluting Bioresorbable Coronary Scaffold (clinicaltrials.gov)
    P=N/A, N=272, Completed, REVA Medical, Inc. | Active, not recruiting --> Completed
    Trial completion
    23d
    Bangle (Zingiber purpureum Rosc.) Extract Ameliorates Colonic Inflammation and Upregulates Autophagy via the Modulation of the AMPK/mTOR/NFκB Pathway in a Mouse Colitis Model. (PubMed, Mol Nutr Food Res)
    Plasma leucine-rich α2-glycoprotein (LRG) levels, macrophage count, and the levels of nuclear factor kappa B (NFκB) p65, tumor necrosis factor-α (TNF-α), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), mechanistic target of rapamycin (mTOR), and autophagy markers were analyzed...Additionally, PGC-1α and phosphorylated AMPK levels were increased, while phosphorylated mTOR levels decreased, and autophagy marker microtubule-associated protein 1 light chain 3B (LC3B)-II levels were increased in the DSS + 3% BaE group. BaE may ameliorate colonic inflammation and upregulate autophagy via the modulation of the AMPK/mTOR/NFκB pathway in DSS-induced colitis.
    Preclinical • Journal
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    TNFA (Tumor Necrosis Factor-Alpha) • MAP1LC3B (Microtubule Associated Protein 1 Light Chain 3 Beta)
    |
    sirolimus
    23d
    Rhus coriaria (Sumac) induces autophagic cell death and inhibits mTOR, p38MAPK and STAT3 pathways in 5fluorouracil-resistant colorectal cancer cells. (PubMed, Front Pharmacol)
    Colorectal cancer is a leading cause of cancer related-death worldwide, and resistance to 5-fluorouracil (5FU, a key component of chemotherapy regimens, is a major clinical concern...Lastly, we confirmed RCE inhibited the growth of both HCT-116-WT and HCT-116-5FU-R xenografts in a chick embryo model. Collectively, our findings highlight that RCE is a source of phytochemicals that can be used as anticancer agents for 5FU-resistant CRC.
    Journal
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    BIRC5 (Baculoviral IAP repeat containing 5) • BAX (BCL2-associated X protein) • CASP7 (Caspase 7) • BECN1 (Beclin 1)
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    5-fluorouracil
    24d
    Discovery of Sirolimus Sensitive Biomarkers in Blood (clinicaltrials.gov)
    P2, N=33, Completed, National Heart, Lung, and Blood Institute (NHLBI) | Active, not recruiting --> Completed
    Trial completion
    |
    sirolimus
    24d
    Vorinostat and Temsirolimus With or Without Radiation Therapy in Treating Younger Patients With Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov)
    P1, N=18, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    Torisel (temsirolimus) • Zolinza (vorinostat)
    24d
    Comparison of the Differences of Peripheral Blood Treg in Patients with Thrombocytopenia of Different Etiologies and the Theraputic Effect and Influence of Sirolimus on Peripheral Treg, T Subgroups and Cytokines (ChiCTR2500097006)
    P=N/A, N=120, Recruiting, Department of Rheumatology and Allergy, Xuanwu Hospital, Capital Medical University; Xuanwu Hospital, Capital Medical University
    New trial
    |
    sirolimus
    24d
    Systematic treatment regiman of nodular sclerosis related renal angiomyolipoma based on surgical intervention (ChiCTR2500095913)
    P=N/A, N=20, Not yet recruiting, West China hospital, Sichuan University; West China hospital, Sichuan University
    New trial
    |
    everolimus
    24d
    Impacts of Mechanistic Target of Rapamycin (mTOR) Inhibition on Aged Human Muscle (Rapamune) (clinicaltrials.gov)
    P=N/A, N=16, Recruiting, University of Nottingham | Trial completion date: May 2024 --> May 2027 | Trial primary completion date: May 2024 --> May 2027
    Trial completion date • Trial primary completion date
    |
    sirolimus
    24d
    The prospect of novel orphan therapeutic protocol for TSC2/PKD1 contiguous gene syndrome: a case report. (PubMed, BMC Nephrol)
    This case illustrates the importance of recognizing overlapping genetic disorders, and providing insights into an innovative therapeutic approach. By integrating detailed clinical assessment with genetic testing, the diagnosis was clarified, and targeted therapies can be selected to address the dual impact of ADPKD and TSC; however, further studies are needed to evaluate the efficacy and safety of this approach. We also emphasize the need to recognize other cases of renal polycystic disease associated with angiomyolipomas and cutaneous manifestations.
    Journal
    |
    TSC2 (TSC complex subunit 2) • PKD1 (Polycystin 1) • PRKD1 (Protein Kinase D1)
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    everolimus
    24d
    miR-221 is a prognostic marker and promotes the proliferation and migration of esophageal squamous cell carcinoma by inhibiting autophagy. (PubMed, Discov Oncol)
    The interaction between miR-221 and autophagy presents a promising therapeutic target for ESCC management.
    Journal
    |
    MIR221 (MicroRNA 221)
    |
    sirolimus
    25d
    The role of endoplasmic reticulum IP(3)R calcium channel in vitamin E succinate induced autophagy of human gastric cancer cell (PubMed, Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi)
    The experiment was set up with solvent control group (0.1% ethanol), VES dose groups, 100 nmol/L rapamycin (RAPA) as autophagy positive control group (RAPA group), 15 μg/ml tunicamycin (TM) was used as the endoplasmic reticulum stress (ERS) positive control group (TM group), 10 μmol/ml 2-aminoethyl diphenylborinate (2-APB group) was used to inhibit IP(3)R (2-APB group) and VES+2-APB group...Compared with VES group, LC3 and Beclin1 protein expressions in two kinds of gastric cancer cells in VES+2-APB groups were significantly decreased (P<0.05) . VES may activate intracellular calcium redistribution through IP(3)R-Grp75-VDAC1 calcium channel and induce autophagy in gastric cancer cells.
    Journal
    |
    MAP1LC3B (Microtubule Associated Protein 1 Light Chain 3 Beta) • BECN1 (Beclin 1) • HSPA9 (Heat Shock Protein Family A (Hsp70) Member ) • RHOD (Ras Homolog Family Member D) • VDAC1 (Voltage Dependent Anion Channel 1)
    |
    sirolimus
    25d
    Tuberous Sclerosis Due to Deletion of Exons 4-8 in TSC2 Gene, Favourably Responding to Phenytoin and Everolimus: A Case Report. (PubMed, Cureus)
    From the age of 19, she also received everolimus, as a result of which the multi-organ hamartomas regressed significantly. This case shows that epilepsy in TSC is not intractable, that phenytoin could be an option for epilepsy in TSC patients, and that everolimus is very effective in terms of regression of benign tumors.
    Journal
    |
    TSC2 (TSC complex subunit 2)
    |
    everolimus
    26d
    The role of the mTOR pathway in breast cancer stem cells (BCSCs): mechanisms and therapeutic potentials. (PubMed, Stem Cell Res Ther)
    Clinical trials investigating mTOR inhibitors like sirolimus and combination therapies with agents such as everolimus and trastuzumab are discussed, underscoring their potential in eradicating BCSCs and improving patient outcomes. In conclusion, targeting the mTOR pathway presents a viable and promising avenue for enhancing breast cancer treatment efficacy by effectively eliminating BCSCs, reducing tumor recurrence, and improving overall patient survival. Continued research and clinical validation of mTOR-targeted therapies are essential to translate these insights into effective clinical interventions, ultimately advancing personalized cancer management and therapeutic outcomes for breast cancer patients.
    Review • Journal
    |
    TGFB1 (Transforming Growth Factor Beta 1) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1)
    |
    Herceptin (trastuzumab) • everolimus • sirolimus
    29d
    Somatic uniparental disomy of PTEN in endothelial cells causes vascular malformations in patients with PTEN Hamartoma Tumor Syndrome. (PubMed, Cancer Discov)
    We established a mouse model of PHTS-related vascular malformations and identified that the mTOR inhibitor rapamycin and AKT inhibitor capivasertib block vascular lesion growth. As proof-of-concept for clinical activity, off-label treatment with rapamycin of two patients with PHTS reduced vascular overgrowth and abrogated lesion-associated pain. Overall, our results uncover the genetic cause of vascular malformations in patients with PHTS and open new avenues for therapeutic intervention.
    Journal
    |
    PTEN (Phosphatase and tensin homolog)
    |
    PTEN mutation
    |
    Truqap (capivasertib) • sirolimus
    29d
    Comparison of mTOR inhibitors combined with endocrine therapy versus that alone in breast cancer: a meta-analysis. (PubMed, Future Oncol)
    This meta-analysis aims to evaluate the efficacy and safety of rapamycin (mTOR) inhibitors with endocrine therapy versus endocrine therapy alone in treating advanced or metastatic estrogen receptor/progesterone receptor (ER/PR) + breast cancer...However, the incidence of adverse events was higher in the combination therapy group, notably stomatitis (p < 0.001), elevated aspartate aminotransferase/alanine aminotransferase (p = 0.04), and diarrhea (p = 0.01). The combination of mTOR inhibitors with endocrine therapy offers superior efficacy with manageable toxicities in patients with advanced or metastatic ER/PR+ breast cancer.
    Retrospective data • Review • Journal
    |
    ER (Estrogen receptor)
    |
    sirolimus
    29d
    CD44 and Its Role in Solid Cancers - A Review: From Tumor Progression to Prognosis and Targeted Therapy. (PubMed, Front Biosci (Landmark Ed))
    CD44 plays a major role in tumor progression, both locally and systemically, by direct interaction with the extracellular matrix, inducing tissue remodeling, activation of different cellular pathways, such as Akt or mechanistic target of rapamycin (mTOR), and stimulation of angiogenesis...In this review, we highlight the properties of CD44, its expression in normal and tumoral tissues through immunohistochemistry and potential treatment options. We also discuss the clinical significance of this marker and its added value in therapeutic decision-making.
    Review • Journal
    |
    mTOR (Mechanistic target of rapamycin kinase) • CD44 (CD44 Molecule) • CD24 (CD24 Molecule) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1)
    |
    sirolimus
    29d
    FAME 3: A Comparison of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Patients With Multivessel Coronary Artery Disease (clinicaltrials.gov)
    P=N/A, N=1500, Active, not recruiting, Stanford University | Trial completion date: Dec 2024 --> Apr 2025
    Trial completion date
    29d
    xCT/Slc7a11 promotes pulmonary arterial hypertension by disrupting AMPKα suppression of mTOR activation. (PubMed, Biochem Pharmacol)
    These findings suggest that xCT promotes the development of PAH, likely through suppression of AMPKα and activation of mTOR. Blockage of xCT and mTOR or activation of AMPKα by existing drugs such as sulfasalazine, sirolimus, and metformin may offer readily therapeutic strategies for PAH.
    Journal
    |
    SLC7A11 (Solute Carrier Family 7 Member 11)
    |
    sirolimus • metformin
    30d
    Defective PINK1-dependent mitophagy is involved in high glucose-induced neurotoxicity. (PubMed, Neuroscience)
    Additionally, cells were exposed to high glucose (50 mM) with or without 100 nM rapamycin (a mitophagy enhancer) for 48 h, or transfected with PINK1 siRNA...Our findings suggest that hyperglycemia-induced disruption of the PINK1/Parkin mitophagy pathway impairs mitochondrial homeostasis, leading to apoptosis. Therefore, targeting PINK1 pathway activation or restoring mitophagy might be a promising therapeutic strategy for PDN treatment.
    Journal
    |
    PTEN (Phosphatase and tensin homolog) • CASP3 (Caspase 3) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
    |
    sirolimus