- |||||||||| everolimus / Generic mfg.
Clinical, Review, Journal: Antiproliferative Systemic Therapies for Metastatic Small Bowel Neuroendocrine Tumours. (Pubmed Central) - Feb 19, 2022 Large randomized clinical trials, with somatostatin analogues (PROMID, CLARINET) or with peptide receptor radionuclide therapy (PRRT) with 177-lutetium (NETTER-1 trial) as well as the mammalian target of rapamycin inhibitor (mTOR) everolimus (RADIANT trials), represent milestones for the medical management of unresectable grade 1 and 2 SBNETS over the last decade...However, multiple unsolved questions remain. This review provides a comprehensive review of the main systemic therapeutic options for advanced SBNETs and discusses the latest guideline recommendations for palliative treatment.
- |||||||||| trimethoprim/sulfamethoxazole / Generic mfg., everolimus / Generic mfg.
Tortured by mTOR Inhibitors? A Case of Pneumocystis Pneumonia Originally Diagnosed as mTOR Pneumonitis (Area F, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_1006; PJP infection can mimic mTOR pneumonitis both clinically and radiographically, and notably, the diagnosis in this case was confirmed with PCR despite two negative DFA smears. This case highlights the need for early bronchoscopy in patients on chronic mTOR therapy with pulmonary infiltrates, as well as the need for PJP PCR studies in addition to DFA testing.
- |||||||||| everolimus / Generic mfg.
Clinical, PK/PD data, Journal, Real-world evidence: Real-world pharmacokinetics and pharmacodynamics of everolimus in metastatic breast cancer. (Pubmed Central) - Feb 17, 2022 Furthermore, the median PFS was numerically longer in patients who maintained a steady-state C below the threshold than in those who did not (327 days [95 % CI 103-355 days] vs. 194 days [95 % CI 45 days-not estimable]; P = 0.35). Conclusions The suggested upper threshold for the therapeutic window of everolimus C was 17.3 ng/mL. Pharmacokinetically guided dosing may improve the efficacy and safety of everolimus for mBC, warranting further investigation in a larger study.Clinical trial registry: Not applicable.
- |||||||||| everolimus / Generic mfg.
Review, Journal, IO biomarker: Bronchial Carcinoids: From Molecular Background to Treatment Approach. (Pubmed Central) - Feb 16, 2022 These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor.
- |||||||||| sirolimus / Generic mfg.
Review, Journal: Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review. (Pubmed Central) - Feb 12, 2022 The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways...This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.
- |||||||||| everolimus / Generic mfg.
Clinical, Journal: Phase 0 Clinical Trial of Everolimus in Patients with Vestibular Schwannoma or Meningioma. (Pubmed Central) - Feb 11, 2022 Everolimus led to incomplete inhibition of mTORC1 and downstream signaling. These data may explain the limited anti-tumor effect of everolimus observed in clinical studies for NF2 patients and will inform the design of future pre-clinical and clinical studies targeting mTORC1 in meningiomas and schwannomas.
- |||||||||| everolimus / Generic mfg., mycophenolate mofetil / Generic mfg.
Review, Journal: Current aspects of renal dysfunction after liver transplantation. (Pubmed Central) - Feb 8, 2022 They are based mainly on delaying the application of CNI during the immediate postoperative-period, reducing their dosage, and associating them with other less nephrotoxic drugs, such as mycophenolate mofetil and everolimus. This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT.
- |||||||||| everolimus / Generic mfg.
Trial completion, Trial primary completion date: RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome (clinicaltrials.gov) - Feb 8, 2022 P1/2, N=46, Completed, This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT. Active, not recruiting --> Completed | Trial primary completion date: Sep 2021 --> Feb 2021
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
RAPALOGS DOWNMODULATE INTRINSIC IMMUNITY AND PROMOTE CELL ENTRY OF SARS-CoV-2 ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_254; In the hamster model of SARS-CoV-2 infection, injection of rapamycin four hours prior to virus exposure resulted in elevated virus titers in lungs, accelerated weight loss, and decreased survival. Our findings indicate that preexisting use of certain rapalogs may elevate host susceptibility to SARS-CoV-2 infection and disease by activating a lysosome-mediated suppression of intrinsic immunity.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), Nexavar (sorafenib) / Bayer, Amgen
Review, Journal: Advances in targeted therapy for osteosarcoma based on molecular classification. (Pubmed Central) - Feb 5, 2022 Therefore, we indicated the importance of molecular classification on the targeted therapy for osteosarcoma. And the stratification of patients based on the genetic characteristics of osteosarcoma will help to obtain a better therapeutic response to targeted therapies, bringing us closer to the era of personalized medicine.
- |||||||||| everolimus / Generic mfg.
Clinical, Journal, IO biomarker: Significant benefit of everolimus in a patient with urothelial bladder cancer harboring a rare M1043I mutation of PIK3CA. (Pubmed Central) - Feb 3, 2022 To our knowledge, this is the first reported case of PIK3CA-mutant UBC for which everolimus therapy demonstrated a significant benefit suggesting that the rare M1043I mutation variant may be a potential biomarker of sensitivity to everolimus. Further insights into its mechanism and clinical studies are needed to clarify the effectiveness of everolimus therapy in patients with PIK3CA M1043I mutation.
- |||||||||| bortezomib / Generic mfg., cisplatin / Generic mfg., paclitaxel / Generic mfg.
Clinical, Journal, Combination therapy: Combination Therapy With Bortezomib in Renal Medullary Carcinoma: A Case Series. (Pubmed Central) - Feb 3, 2022 Given the extremely rare nature of this disease and dismal prognosis, new treatment modalities should be pursued, and whenever possible, patients should be enrolled in a clinical trial. We propose that a multiinstitution clinical trial of this regiment may be warranted.
- |||||||||| everolimus / Generic mfg.
Trial completion date, Trial primary completion date: Everolimus for Children With Recurrent or Progressive Ependymoma (clinicaltrials.gov) - Feb 2, 2022 P2, N=11, Active, not recruiting, We propose that a multiinstitution clinical trial of this regiment may be warranted. Trial completion date: Dec 2021 --> Jul 2022 | Trial primary completion date: Dec 2021 --> Jul 2022
- |||||||||| cisplatin / Generic mfg., sirolimus / Generic mfg.
Journal: Jolkinolide B sensitizes bladder cancer to mTOR inhibitors via dual inhibition of Akt signaling and autophagy. (Pubmed Central) - Feb 2, 2022 A mechanistic study revealed that JB induced a dual inhibition of Akt feedback activation and cytoprotective autophagy, potentiating the anti-proliferative efficacy of mTORi in both PTEN-deficient and cisplatin-resistant bladder cancer cells...These synergistic mechanisms are related to cellular reactive oxygen species accumulation. Our study suggests that dual inhibition of Akt feedback activation and cytoprotective autophagy is an effective strategy in mTORi-based therapy, and JB + mTORi combination associated with multiple anti-cancer mechanisms and good tolerance in mouse models may serve as a promising treatment for bladder cancer.
- |||||||||| everolimus / Generic mfg.
Journal: Possible effects of sirolimus treatment on the long‑term efficacy of COVID‑19 vaccination in patients with β‑thalassemia: A theoretical perspective. (Pubmed Central) - Feb 2, 2022 For instance, short‑term treatment with mammalian target of rapamycin inhibitors (such as everolimus and sirolimus) has been found to improve responses to influenza vaccination in adults, with benefits possibly persisting for a year following treatment...In the present study, the authors present the hypothesis that sirolimus treatment, in addition to its beneficial effects on erythroid‑related parameters, may play a crucial role in sustaining the effects of COVID‑19 vaccination in patients with β‑thalassemia. This hypothesis is based on several publications demonstrating the effects of sirolimus treatment on the immune system.
- |||||||||| everolimus / Generic mfg.
Preclinical, Journal: Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats. (Pubmed Central) - Feb 1, 2022 This hypothesis is based on several publications demonstrating the effects of sirolimus treatment on the immune system. Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce neuronal apoptosis and microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on seizure-induced brain damage.
- |||||||||| Torisel (temsirolimus) / Pfizer
Licensing / partnership, Journal: In silico development of new PET radiopharmaceuticals from mTOR inhibitors. (Pubmed Central) - Feb 1, 2022 Molecular docking results also helped us to eliminate molecules that did not interact correctly with the target. Finally, we found for the first time, that the novel compounds synthesized through the electrophilic addition reaction that employed F-selectfluor, should maintain the biological activity of original compounds and could be suitable as Positron Emission Tomography radiopharmaceuticals targeting mTOR Complex1 system.
- |||||||||| everolimus / Generic mfg.
Trial completion date, Trial termination, Trial primary completion date, Combination therapy: Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score (clinicaltrials.gov) - Feb 1, 2022 P2, N=17, Terminated, Finally, we found for the first time, that the novel compounds synthesized through the electrophilic addition reaction that employed F-selectfluor, should maintain the biological activity of original compounds and could be suitable as Positron Emission Tomography radiopharmaceuticals targeting mTOR Complex1 system. Trial completion date: Nov 2020 --> Mar 2021 | Completed --> Terminated | Trial primary completion date: Nov 2020 --> Mar 2021; Phase 2 of recruitment was contingent on 5 of 15 patients responding, which did not occur.
- |||||||||| everolimus / Generic mfg.
Journal: Impaired myelin production due to an intrinsic failure of oligodendrocytes in mTORpathies. (Pubmed Central) - Jan 29, 2022 Results obtained in patient-derived primary oligodendroglial and TSC2 knock-out cells suggest that maturation of oligodendroglia and production of a proper myelin sheath seem to be impaired as a result of mTOR pathway disturbance. Hence, oligodendroglial pathology may reflect a more direct effect of the abnormal genetic program rather than to be an inactive bystander of chronic epilepsy.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Clinical, Journal: Clinical Importance of Plasma Drug Concentration of Oral Molecular Targeted Drugs for Renal Cell Carcinoma. (Pubmed Central) - Jan 29, 2022 This study demonstrated that systemic concentrations of oral molecular targeted drugs for RCC were considered to be clinically useful for dose adjustment, monitoring of treatment adherence, and the detection of drug interactions. Moreover, this information could be successfully used to guide individualized therapy to maximize the antitumor effects of these drugs.
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