- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Evidence for Bell-Shaped Dose-Response Emetic Effects of Temsirolimus and Analogs: The Broad-Spectrum Antiemetic Efficacy of a Large Dose of Temsirolimus Against Diverse Emetogens in the Least Shrew (Cryptotis parva). (Pubmed Central) - Apr 22, 2022 With its analogs (everolimus, ridaforolimus, and rapamycin), it forms a group of anticancer agents that block the activity of one of the two mammalian targets of rapamycin (mTOR) complexes, mTORC1...We then determined the broad-spectrum antiemetic potential of a 20 mg/kg (i.p.) dose of temsirolimus against diverse emetogens, including selective and nonselective agonists of 1) dopaminergic D receptors (apomorphine and quinpirole); 2) serotonergic 5-HT receptors [5-HT (serotonin) and 2-methyl-5-HT]; 3) cholinergic M receptors (pilocarpine and McN-A-343); 4) substance P neurokinin NK receptors (GR73632); 5) the L-type calcium (Ca) channel (LTCC) (FPL64176); 6) the sarcoplasmic endoplasmic reticulum Ca ATPase inhibitor, thapsigargin; 7) the CB receptor inverse agonist/antagonist, SR141716A; and 8) the chemotherapeutic cisplatin...The mechanisms underlying the pro- and antiemetic effects of temsirolimus evaluated by immunochemistry for c-fos expression demonstrated a c-fos induction in the AP and NTS, but not DMNX with the 10 mg/kg emetic dose of temsirolimus, whereas its larger antiemetic dose (20 mg/kg) had no significant effect. Our study is the first to provide preclinical evidence demonstrating the promising antiemetic potential of high doses of temsirolimus and possibly its analogs in least shrews.
- |||||||||| Optimal Treatment Options for High Risk ER+ Breast Cancer (RM 3(Walker Hall 1)) - Apr 22, 2022 - Abstract #GBCC2022GBCC_136;
These agents with standard endocrine therapy have been already planned.Up to now the available clinical and genomic tools are not capable to accurately identify those patients at high risk who will eventually relapse and are also not precise predictive factors for response to systemic therapies (endocrine therapy, chemotherapy).Although residual disease after neoadjuvant treatment can be easily identified if macroscopic, minimal residual disease that can be responsible for late recurrences is difficult to detect. The use of liquid biopsies can help us in the future to identify those patients that can have additional treatment where there is still very low tumor burden.
- |||||||||| Piqray (alpelisib) / Novartis, Keytruda (pembrolizumab) / Merck (MSD)
Various Targeted Therapies for Advanced ER+/HER- Breast Cancer: To Whom Should We Give Which? (RM 1(Vista 1+2)) - Apr 22, 2022 - Abstract #GBCC2022GBCC_6; Ongoing research efforts are focused on understanding mechanisms of resistance to CDK4/6 inhibitors, developing novel endocrine agents with or without CDK4/6 inhibitors, novel targeted therapies, and evaluating the role of antibody drug conjugates for this subtype of breast cancer. Data from the ongoing phase 3 trials evaluating triplet combinations and antibody drug conjugates in the metastatic setting are eagerly awaited and have the potential to further change the treatment paradigm of HR+/HER2- MBC.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), Torisel (temsirolimus) / Pfizer
Select Rapamycin Analogs Promote VSV-G-Mediated Cell Entry by Activating TFEB-Dependent Microautophagy (Poster Board Number: W-265; Hall D) - Apr 20, 2022 - Abstract #ASGCT2022ASGCT_1039; Our findings suggest that they act at the level of cell-intrinsic immunity to undermine the cell's first line of antiviral defenses. The development of rapamycin analogs that lack this activity may reduce unintended immunosuppression in human subjects.
- |||||||||| Simulect (basiliximab) / Novartis
SEVERE IMMUNE CHECKPOINT INHIBITOR ASSOCIATED HEPATITIS SUCCESSFULLY TREATED WITH BASILIXIMAB () - Apr 20, 2022 - Abstract #ASPHO2022ASPHO_395; First line therapy remains discontinuation of the ICI and initiation of steroids, with some literature supporting T-cell-specific immunomodulators such as mycophenolate, tacrolimus, or azathioprine as second line agents...Design/ Case ReportA 22-year-old female with recurrent metastatic osteosarcoma of her right proximal tibia began treatment with the anti-PD-1 monoclonal antibody nivolumab for refractory disease...Given continued elevation in her LFTs, further treatments included everolimus, rabbit ATG, and tacrolimus, none of which were successful in persistently decreasing her LFTs, which peaked at greater than 20 times normal, indicating a Grade 4 adverse event... Basiliximab may be an effective therapy for steroid-resistant severe ICI associated hepatitis.
- |||||||||| dexamethasone / Generic mfg., everolimus / Generic mfg.
Journal: mTOR inhibition downregulates glucose-6-phosphate dehydrogenase and induces ROS-dependent death in T-cell acute lymphoblastic leukemia cells. (Pubmed Central) - Apr 20, 2022 In vivo studies of NOD/SCID mice inoculated with refractory T-ALL PDX demonstrated that everolimus overcame dexamethasone resistance in conditions of high tumor burden that mimicked the clinical setting of acute leukemia. These findings provide insight into the crosstalk between mTOR and ROS homeostasis in T-ALL cells and furnish mechanistic evidence to support the combination of glucocorticoids with mTOR inhibitors as a therapeutic avenue for treating refractory T-ALL.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS
Biomarker, Clinical, Journal, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker: The Significance of PARP1 as a biomarker for Predicting the Response to PD-L1 Blockade in Patients with PBRM1-mutated Clear Cell Renal Cell Carcinoma. (Pubmed Central) - Apr 19, 2022 By contrast, for patients treated with everolimus (n = 130) there was no significant difference by PARP1 status for progression-free survival (PFS; p = 0.9) or OS (p = 0.38)...PATIENT SUMMARY: Immune checkpoint inhibitors (ICIs) are key agents in the treatment of multiple cancers. We found that expression of the PARP1 protein was associated with survival after ICI treatment and with the response to ICI treatment in patients with clear cell kidney cancer who have a mutation of the PBRM1 gene.
- |||||||||| Torisel (temsirolimus) / Pfizer, Jevtana (cabazitaxel) / Sanofi, Emcure
Biomarker, Journal, BRCA Biomarker: Bioinformatics Screening of Potential Biomarkers from mRNA Expression Profiles to Discover Drug Targets and Agents for Cervical Cancer. (Pubmed Central) - Apr 19, 2022 Finally, we investigated the binding stability of the top-ranked three drugs (Paclitaxel, Vincristine, Vinorelbine) by using 100 ns MD-based MM-PBSA simulations with the three top-ranked proposed receptors (AURKA, CDK1, TOP2A) and observed their stable performance. Therefore, the proposed drugs might play a vital role in the treatment against CC.
- |||||||||| Signifor (pasireotide) / Recordati, Sutent (sunitinib) / Pfizer
Retrospective data, Journal: Target therapies plus somatostatin analogues in NETs: a network meta-analysis. (Pubmed Central) - Apr 15, 2022 The role of pasireotide should be explored in selected subgroups of patients. Last, the combination of everolimus and octreotide appears promising and should be more widely considered in clinical practice.
- |||||||||| everolimus / Generic mfg.
Clinical, Journal: A pilot study of everolimus and radiation for neuroendocrine liver metastases. (Pubmed Central) - Apr 15, 2022 In conclusion, combined everolimus and radiation is well-tolerated for neuroendocrine liver metastases and is associated with excellent local control. The approach of selective local ablation of oligometastatic or oligoprogressive disease warrants further evaluation in this patient population.
- |||||||||| everolimus / Generic mfg.
Review, Journal: Perfect match: mTOR inhibitors and tuberous sclerosis complex. (Pubmed Central) - Apr 14, 2022 Although mTOR inhibitors (rapamycin/everolimus) demonstrate great potential in TSC management, two major concerns hamper their generalized application...Thus, indicators are required to effectively predict the efficacy of mTOR inhibitors. Herein, we have summarized the current utilization of mTOR inhibitors in the treatment of TSC and focused on their efficacy and safety, in an attempt to provide a reference to guide the treatment of TSC.
- |||||||||| Lumakras (sotorasib) / Amgen
Trial completion date, Trial primary completion date, Combination therapy, Monotherapy, Metastases: CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - Apr 14, 2022 P1b/2, N=1054, Recruiting, Herein, we have summarized the current utilization of mTOR inhibitors in the treatment of TSC and focused on their efficacy and safety, in an attempt to provide a reference to guide the treatment of TSC. Trial completion date: Jan 2027 --> Aug 2026 | Trial primary completion date: Jan 2024 --> Aug 2024
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD), gedatolisib (PF-05212384) / Celcuity, Torisel (temsirolimus) / Pfizer
Journal: Structural Aspects of mTOR Inhibitors: In Progress to Search Potential Compounds. (Pubmed Central) - Apr 13, 2022 The mTOR inhibitors bearing heterocyclic moieties such as quinazoline, thiophene, morpholine, imidazole, pyrazine, furan, quinoline are under investigation against various cancer cell lines (U87MG, PC-3, MCF-7, A549, MDA-231). In this review, we summarized updated research related to mTOR inhibitors, their structure-activity relationship which may help scientists for the development of potent inhibitors against cancer.
- |||||||||| everolimus / Generic mfg.
Journal: The expression and significance of p4E-BP1/4E-BP1 in prostate cancer. (Pubmed Central) - Apr 13, 2022 In this review, we summarized updated research related to mTOR inhibitors, their structure-activity relationship which may help scientists for the development of potent inhibitors against cancer. These findings suggest that p4E-BP1 is a potential biomarker and therapy target for prostate cancer, and patients with high expressions of p4E-BP1 may benefit from Everolimus treatment.
- |||||||||| lenvatinib / Generic mfg.
Journal: Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies. (Pubmed Central) - Apr 13, 2022 Collectively, the data provide the rationale to start lenvatinib at the recommended doses and then interrupt or dose reduce as necessary to achieve required dose intensity for maximized patient benefit. The adverse-event profile of lenvatinib is consistent with that of other tyrosine kinase inhibitors, and clinicians are encouraged to review and adopt relevant symptom-management strategies.
- |||||||||| letrozole / Generic mfg., everolimus / Generic mfg.
Trial primary completion date, Metastases: Letrozole and RAD001 With Advanced or Recurrent Endometrial Cancer (clinicaltrials.gov) - Apr 13, 2022 P2, N=31, Active, not recruiting, The present results suggest that the addition of gemcitabine with or without navitoclax to everolimus is a promising strategy that warrants further evaluation in future clinical trials for malignant meningioma. Trial primary completion date: Apr 2021 --> Apr 2022
- |||||||||| everolimus / Generic mfg.
Journal: Role of mTOR Pathway in Modulation of Radiation Induced Bystander Effects. (Pubmed Central) - Apr 12, 2022 These results suggested that mTOR pathway plays an important role in RIBEs. These effects are cell type specific depending on the radiosensitivity of the target cells and the therapeutic benefits of radiation may be modulated by treatment with mTOR inhibitors.
- |||||||||| Solucin (177Lu-edotreotide) / ITM Isotopen Technologien Munchen
Enrollment closed: COMPETE: Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients (clinicaltrials.gov) - Apr 12, 2022 P3, N=302, Active, not recruiting, The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI. Recruiting --> Active, not recruiting
- |||||||||| lenvatinib / Generic mfg.
Clinical, Journal: Lenvatinib-related renal microangiopathy: a case series. (Pubmed Central) - Apr 9, 2022 The best therapy in these patients is still uncertain. Earlier and more precise measurement of urine protein levels, allowing for early dose adjustment, could be effective in preventing further damage and drug discontinuation.
- |||||||||| tacrolimus intravenous / Generic mfg., everolimus / Generic mfg.
Clinical, Journal: Immunosuppression in patients with Grade 3 Acute-On-Chronic Liver Failure at transplantation: A practice analysis study. (Pubmed Central) - Apr 9, 2022 Tacrolimus IPV < 40% (P = .019), absence of early tacrolimus overdose (P = .033), use of anti-IL2-receptor antibodies (P = .034), and early mycophenolic acid introduction (P = .038) predicted 1-year survival...Early everolimus introduction was neither associated with higher rejection rates nor with more surgical complications...Occurrence and treatment of rejection impacts on survival. Early introduction of mTOR inhibitor seems safe and efficient in this situation.
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