^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG:

    everolimus

    i
    Other names: RAD, RAD001, SDZ RAD, RAD 001
    Company:
    Generic mfg.
    Drug class:
    mTOR inhibitor
    Related drugs:
    3d
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1/2, N=1126, Recruiting, Amgen | Trial primary completion date: Sep 2026 --> Dec 2026
    Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    4d
    ADELA: Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i. (clinicaltrials.gov)
    P3, N=240, Not yet recruiting, MedSIR
    New P3 trial • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 mutation • ER mutation • ESR1 mutation • CDK4 mutation
    |
    everolimus • dexamethasone • Orserdu (elacestrant)
    5d
    LITMMUS-UCSF: Liver Transplantation With Tregs at UCSF (clinicaltrials.gov)
    P1/2, N=42, Terminated, National Institute of Allergy and Infectious Diseases (NIAID) | N=30 --> 42
    Enrollment change
    |
    everolimus • cyclophosphamide
    11d
    Rapid Sequencing of Approved Therapies in Patients With Metastatic or Unresectable Clear Cell Renal Cell Carcinoma (clinicaltrials.gov)
    P1, N=20, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • everolimus • Lenvima (lenvatinib) • Cabometyx (cabozantinib tablet)
    12d
    Lenvatinib and Everolimus in Renal Cell Carcinoma (RCC) (clinicaltrials.gov)
    P1, N=11, Active, not recruiting, Yousef Zakharia | Trial completion date: Sep 2024 --> Jun 2028
    Trial completion date • Metastases
    |
    everolimus • Lenvima (lenvatinib)
    13d
    Diagnosis and management of neuroendocrine tumours. (PubMed, Clin Med (Lond))
    Treatment comprises surgery where curative resection is possible through to approaches where disease stabilisation is the key, involving somatostatin analogues, peptide receptor radionuclide therapy (PRRT), everolimus, sunitinib, liver-directed therapies and sometimes chemotherapy. Although local and systemic complications can occur, they are associated with reasonable 5- and 10-year survival rates, respectively.
    Journal
    |
    SSTR (Somatostatin Receptor)
    |
    Sutent (sunitinib) • everolimus
    15d
    Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas. (PubMed, Pharmacol Res)
    When the tumors have metastasized, systemic therapy with protein-tyrosine kinase antagonists including sorafenib, sunitinib, pazopanib, and tivozanib that target vascular endothelial, platelet-derived, fibroblast, hepatocyte, and stem cell factor growth factor receptors (VEGFR, PDGFR, FGFR, MET, and Kit) were prescribed after 2005. The monoclonal antibody immune checkpoint inhibitor nivolumab (targeting PD1) was approved for the treatment of RCCs in 2015. It is usually used now in combination with ipilimumab (targeting CTLA-4) or cabozantinib (a multikinase blocker). Other combination therapies include pembrolizumab (targeting programed cell death protein 1) and axitinib (a VEGFR and PDGFR blocker) or lenvatinib (a multikinase inhibitor). Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors.
    Review • Journal
    |
    FGFR (Fibroblast Growth Factor Receptor)
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Yervoy (ipilimumab) • sorafenib • Sutent (sunitinib) • everolimus • Lenvima (lenvatinib) • Bavencio (avelumab) • Votrient (pazopanib) • Cabometyx (cabozantinib tablet) • Torisel (temsirolimus) • Inlyta (axitinib) • Welireg (belzutifan) • Fotivda (tivozanib)
    16d
    Study of Ribociclib and Everolimus in HGG and DIPG (clinicaltrials.gov)
    P2, N=100, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Jan 2034 --> May 2034 | Initiation date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2028 --> May 2028
    Trial completion date • Trial initiation date • Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)
    |
    PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation
    |
    everolimus • Kisqali (ribociclib)
    19d
    Discovery of a long half-life AURKA inhibitor to treat MYC-amplified solid tumors as a monotherapy and in combination with everolimus. (PubMed, Mol Cancer Ther)
    Aurora kinase inhibitors such as alisertib can destabilize MYC-family oncoproteins and have demonstrated compelling anti-tumor efficacy. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC- driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC- and/or N-MYC.
    Journal • Combination therapy
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
    |
    MYC amplification • MYC overexpression • MYC expression
    |
    everolimus • alisertib (MLN8237)
    21d
    Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE (clinicaltrials.gov)
    P3, N=202, Recruiting, ITM Solucin GmbH | Trial completion date: Sep 2026 --> Sep 2027 | Trial primary completion date: Sep 2024 --> Jun 2027
    Trial completion date • Trial primary completion date • Patient reported outcomes
    |
    SSTR (Somatostatin Receptor)
    |
    SSTR positive
    |
    5-fluorouracil • everolimus • temozolomide • capecitabine • oxaliplatin • leucovorin calcium • Solucin (177Lu-edotreotide)
    21d
    ETV6-NTRK2 Fusion in a Patient With Metastatic Pulmonary Atypical Carcinoid Successfully Treated With Entrectinib: A Case Report and Review of the Literature. (PubMed, Clin Lung Cancer)
    After pursuing other alternative treatments, including chemotherapy (ie, carboplatin, etoposide, capecitabine, temozolomide, and paclitaxel), everolimus, and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. To date, she has maintained sustained benefit for at least 1 year from initiation of entrectinib. Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.
    Review • Journal • PD(L)-1 Biomarker • Metastases
    |
    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • SSTR (Somatostatin Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK2 fusion • ETV6-NTRK2 fusion • NTRK positive • SSTR Expression
    |
    Tecentriq (atezolizumab) • carboplatin • Rozlytrek (entrectinib) • paclitaxel • everolimus • temozolomide • capecitabine • etoposide IV
    22d
    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
    |
    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)
    |
    ER positive • HER-2 negative • PIK3CA mutation • PTEN expression • AKT1 mutation • MTOR mutation
    |
    everolimus
    22d
    Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex? (PubMed, Neuropathol Appl Neurobiol)
    Our study demonstrates that EGFR suppression might be an effective alternative treatment option for SEGAs and tubers, as well as other mTOR-associated malformations of cortical development, including FCD2B.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
    |
    EGFR expression • EGFR overexpression
    |
    Gilotrif (afatinib) • everolimus
    23d
    Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040? (PubMed, World J Transplant)
    The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.
    Journal
    |
    AFP (Alpha-fetoprotein)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • everolimus
    24d
    Feature Engineering-Assisted Drug Repurposing on Disease-Drug Transcriptome Profiles in Gastric Cancer. (PubMed, Assay Drug Dev Technol)
    Then, using the drug repurposing method with the Connectivity Map CLUE Query tools, potential drugs such as Forskolin, Gestrinone, Cediranib, Apicidine, and Everolimus, which showed a highly negative correlation with the expression levels of the selected genes, were identified. This study provides a method to develop new approaches to diagnosing and treating gastric cancer by comparing the transcriptome profiles of patients gastric cancer and performing a feature engineering-assisted drug repurposing analysis based on cancer data.
    Journal
    |
    ETV3 (ETS Variant Transcription Factor 3)
    |
    everolimus • Recentin (cediranib)
    26d
    NCI-2018-01284: A Phase II, Two-Arm Study of Everolimus and Letrozole, +/- Ribociclib (Lee011) in Patients With Advanced or Recurrent Endometrial Carcinoma (clinicaltrials.gov)
    P2, N=90, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    CTNNB1 mutation
    |
    everolimus • Kisqali (ribociclib) • letrozole
    26d
    Optimal targeting of PI3K-AKT and mTOR in advanced oestrogen receptor-positive breast cancer. (PubMed, Lancet Oncol)
    Approvals for oestrogen receptor-positive advanced breast cancer include the PI3K inhibitor alpelisib for PIK3CA-mutated tumours, the AKT inhibitor capivasertib for tumours with alterations in PIK3CA, AKT1, or PTEN, and the mTOR inhibitor everolimus, which is used irrespective of mutation status. The availability of different inhibitors leaves physicians with a potentially challenging decision over which of these therapies should be used for individual patients and when. In this Review, we present a comprehensive summary of our current understanding of the pathways and the three inhibitors and discuss strategies for the optimal sequencing of therapies in the clinic, particularly after progression on a CDK4/6 inhibitor.
    Review • Journal • Metastases
    |
    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    ER positive • PIK3CA mutation • PTEN mutation
    |
    everolimus • Piqray (alpelisib) • Truqap (capivasertib)
    27d
    A Real-world Study of Everolimus Plus Aromatase Inhibitor in Hormone Receptor-positive, HER2-negative Advanced Breast Cancer. (PubMed, Anticancer Res)
    These real-life data show that everolimus in combination with AI in patients with HER2-negative, HR-positive advanced breast cancer is an effective treatment with an acceptable toxicity profile.
    Journal • Real-world evidence • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HR positive • HER-2 negative • HR positive + HER-2 negative • PTEN mutation + HR positive
    |
    everolimus • exemestane
    28d
    Characterizing the Efficacy and Safety of Chemotherapy Plus Everolimus in HER2-Negative Metastatic Breast Cancer Harboring Altered PI3K/AKT/mTOR. (PubMed, Discov Med)
    The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NF1 (Neurofibromin 1) • CDK4 (Cyclin-dependent kinase 4)
    |
    HR positive • HER-2 negative • NF1 mutation
    |
    everolimus • vinorelbine tartrate
    1m
    Tacrolimus and Personalized Therapy to Prevent Acute Rejection Episodes (clinicaltrials.gov)
    P=N/A, N=25, Recruiting, Fondazione IRCCS Policlinico San Matteo di Pavia
    New trial
    |
    everolimus • sirolimus
    1m
    A Trial Evaluating the Activity and Safety of Combination Between Cabozantinib and Temozolomide in Lung and GEP-NENS Progressive After Everolimus, Sunitinib or PRRT (CABOTEM) (clinicaltrials.gov)
    P2, N=35, Recruiting, National Cancer Institute, Naples | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date
    |
    Sutent (sunitinib) • everolimus • temozolomide • Cabometyx (cabozantinib tablet)
    1m
    Rapalog Pharmacology (RAP PAC) Study (clinicaltrials.gov)
    P1, N=72, Recruiting, University of Wisconsin, Madison | Not yet recruiting --> Recruiting
    Enrollment open
    |
    everolimus • sirolimus
    1m
    EMBER: A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer (clinicaltrials.gov)
    P1, N=500, Active, not recruiting, Eli Lilly and Company | Phase classification: P1a/1b --> P1
    Phase classification • Combination therapy • Metastases
    |
    ER (Estrogen receptor)
    |
    HER-2 negative • EGFR positive
    |
    Herceptin (trastuzumab) • everolimus • Perjeta (pertuzumab) • Piqray (alpelisib) • Verzenio (abemaciclib) • exemestane • imlunestrant (LY3484356)
    1m
    A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread (clinicaltrials.gov)
    P1, N=198, Active, not recruiting, Eli Lilly and Company | Phase classification: P1b --> P1
    Phase classification • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6)
    |
    HR positive • HER-2 negative • EGFR positive
    |
    Herceptin (trastuzumab) • everolimus • tamoxifen • Perjeta (pertuzumab) • Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • exemestane • samotolisib (LY3023414)
    1m
    Exemestane plus everolimus and palbociclib in metastatic breast cancer: clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial. (PubMed, Nat Commun)
    Multi-omics data from the phase IIa patients (n = 24 tumor/17 blood biopsy exomes; n = 27 tumor transcriptomes) showed potential mechanisms of resistance (convergent evolution of HER2 activation, BRAFV600E), identified joint genomic/transcriptomic resistance features (ESR1 mutations, high estrogen receptor pathway activity, and a Luminal A/B subtype; ERBB2/BRAF mutations, high RTK/MAPK pathway activity, and a HER2-E subtype), and provided hypothesis-generating results suggesting that mTOR pathway activation correlates with response to the trial's therapy. Our results illustrate how genome and transcriptome sequencing may help better identify patients likely to respond to CDK4/6i therapies.
    P1/2 data • Clinical Trial,Phase I • Clinical Trial,Phase II • Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor)
    |
    BRAF V600E • BRAF V600 • HER-2 mutation • ER mutation • ESR1 mutation
    |
    Ibrance (palbociclib) • everolimus • exemestane
    1m
    LUMEN-1: 177Lu-DOTATATE for Recurrent Meningioma (clinicaltrials.gov)
    P2, N=135, Not yet recruiting, European Organisation for Research and Treatment of Cancer - EORTC
    New P2 trial
    |
    Avastin (bevacizumab) • Sutent (sunitinib) • everolimus • hydroxyurea • Lutathera (lutetium Lu 177 dotatate) • Sandostatin LAR Depot (octreotide acetate)
    1m
    Fruquintinib Plus Everolimus as 2nd Line Therapy of ccRCC Patients Progressed Post IO and TKI Therapy (clinicaltrials.gov)
    P=N/A, N=36, Recruiting, Peking University First Hospital
    New trial • Combination therapy
    |
    everolimus • Fruzaqla (fruquintinib)
    1m
    Phase IV Study of the Safety and Efficacy of Everolimus in Adult Patients With Progressive pNET in China (clinicaltrials.gov)
    P4, N=61, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Feb 2024 | Trial primary completion date: Dec 2024 --> Feb 2024
    Trial completion • Trial completion date • Trial primary completion date • Metastases
    |
    everolimus
    1m
    DFF332 as a Single Agent and in Combination With Everolimus & Immuno-Oncology Agents in Advanced/Relapsed Renal Cancer & Other Malignancies (clinicaltrials.gov)
    P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2025 --> Feb 2025 | Trial primary completion date: Jul 2025 --> Feb 2025
    Trial completion date • Trial primary completion date • Combination therapy • IO biomarker • Metastases • Immuno-oncology
    |
    VHL (von Hippel-Lindau tumor suppressor) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • EPAS1 (Endothelial PAS domain protein 1) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • SDHAF2 (Succinate Dehydrogenase Complex Assembly Factor 2)
    |
    VHL mutation • SDHB mutation
    |
    everolimus • spartalizumab (PDR001) • DFF332 • taminadenant (NIR178)
    2ms
    Everolimus Combined With PD-1 in Advanced Colorectal Cancer Patients (clinicaltrials.gov)
    P2, N=25, Not yet recruiting, Fudan University
    New P2 trial • Tumor mutational burden • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    everolimus
    2ms
    Implantable Microdevice for the Delivery of Drugs and Their Effect on Tumors in Patients With Metastatic or Recurrent Sarcoma (clinicaltrials.gov)
    P1, N=20, Not yet recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    everolimus • temozolomide • doxorubicin hydrochloride • Votrient (pazopanib) • cyclophosphamide • ifosfamide • irinotecan • Torisel (temsirolimus) • vincristine • daunorubicin • ganitumab (AMG 479)
    2ms
    Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study. (PubMed, Int J Cancer)
    The BRAWO study provides real-world evidence of efficacy and safety of EVE + EXE in patients with HR+, HER2- ABC. A high BMI and the absence of visceral metastases were independent predictors of PFS in this cohort of patients.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HR positive • HER-2 negative • PTEN mutation + HR positive
    |
    everolimus • exemestane
    2ms
    SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov)
    P1, N=396, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • everolimus • Verzenio (abemaciclib) • Kisqali (ribociclib) • Truqap (capivasertib) • anastrozole • camizestrant (AZD9833)
    2ms
    Glucose Metabolism in Acute Myeloid Leukemia Cell Line Is Regulated via Combinational PI3K/AKT/mTOR Pathway Inhibitors. (PubMed, Iran J Pharm Res)
    HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination. A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.
    Preclinical • Journal
    |
    HIF1A (Hypoxia inducible factor 1, alpha subunit) • HK2 (Hexokinase 2) • PKM (Pyruvate Kinase M1/2)
    |
    everolimus • Zydelig (idelalisib) • MK-2206
    2ms
    Targeting ERBB2 and PIK3R1 as a therapeutic strategy for dilated cardiomyopathy: A single-cell sequencing and mendelian randomization analysis. (PubMed, Heliyon)
    We found that everolimus was a pharmacological inhibitor for both PIK3R1 and ERBB2...In addition, there is a cross-expression of PIK3R1 and ERBB2 genes in both DCM and tumors. The adaptive immune system and PIK3R1 may be involved in DCM disease progression, while ERBB2 exerts a protective effect against DCM.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
    |
    HER-2 expression • ROS1 expression
    |
    everolimus
    2ms
    Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)
    P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual
    Trial termination
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • Sutent (sunitinib) • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide capsule) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical
    2ms
    PREPARE-iVAC Trial (clinicaltrials.gov)
    P4, N=110, Completed, University Medical Center Groningen | Active, not recruiting --> Completed
    Trial completion
    |
    everolimus
    2ms
    A Study to Learn About the Study Medicine Called PF-07220060 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment (clinicaltrials.gov)
    P3, N=510, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    HER-2 negative
    |
    everolimus • fulvestrant • exemestane • atirmociclib (PF-07220060)
    2ms
    ELIMINATE: Expanding Liver Transplant Immunosuppression Minimization Via Everolimus (clinicaltrials.gov)
    P2, N=340, Not yet recruiting, National Institute of Allergy and Infectious Diseases (NIAID)
    New P2 trial
    |
    everolimus
    2ms
    Fulvestrant and everolimus efficacy after CDK4/6 inhibitor: a prospective study with circulating tumor DNA analysis. (PubMed, Oncogene)
    ctDNA detection at baseline and PIK3CA mutation had an adverse prognostic impact on PFS and OS in multivariate analysis. This prospective cohort study documents the efficacy of fulvestrant and everolimus in CDK4/6i-pretreated ER + /HER2- mBC and highlights the clinical validity of early ctDNA changes as pharmacodynamic biomarker.
    Journal • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 negative • PIK3CA mutation
    |
    everolimus • fulvestrant
    2ms
    ENABLAR-2: Efficacy & Safety Evaluation of Enobosarm in Combo With Abemaciclib in Treatment of ER+HER2- Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=5, Terminated, Veru Inc. | N=186 --> 5
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • everolimus • Verzenio (abemaciclib) • fulvestrant • exemestane • Ostarine (enobosarm)
    2ms
    Design, synthesis and biological evaluation of novel morpholinopyrimidine-5-carbonitrile derivatives as dual PI3K/mTOR inhibitors. (PubMed, RSC Med Chem)
    The most promising compounds 12b and 12d exhibited excellent antitumor activity against the leukemia SR cell line, which is the most sensitive cell line, with IC50 0.10 ± 0.01 and 0.09 ± 0.01 μM, respectively, along with significant effects on PI3Kα/PI3Kβ/PI3Kδ with IC50 values of 0.17 ± 0.01, 0.13 ± 0.01 and 0.76 ± 0.04 μM, respectively, for 12b and 1.27 ± 0.07, 3.20 ± 0.16 and 1.98 ± 0.11, respectively, for 12d compared to LY294002. Compared to Afinitor, these compounds inhibited mTOR with IC50 values of 0.83 ± 0.05 and 2.85 ± 0.17 μM, respectively...Compounds 12b and 12d also caused a G2/M cell cycle arrest in the leukaemia SR cell line. The findings of this study indicate that the highest effect was observed for 12b, which was supported by western blot and docking analysis.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) • ANXA5 (Annexin A5)
    |
    everolimus • LY294002