- |||||||||| Torisel (temsirolimus) / Pfizer
Preclinical, Journal: Anti-tumor effects of cryptotanshinone (CHO) in human osteosarcoma cell lines. (Pubmed Central) - Jun 8, 2022
Specifically, Cryptotanshinone in combination with Temsirolimus inhibit the JAK/STAT, MAPK/ERK, and PI3K/Akt/mTOR pathways and induce cell death in tumor cells. We corroborated our theoretical predictions using wet-lab experiments on SaOS2, 143B, G292, and HU03N1 human osteosarcoma cell lines, thereby demonstrating the potency of Cryptotanshinone in fighting osteosarcoma.
- |||||||||| Inlyta (axitinib) / Pfizer, Torisel (temsirolimus) / Pfizer, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Biomarker, Journal, PD(L)-1 Biomarker, IO biomarker: B7-H4 Immune Checkpoint Protein Affects Viability and Targeted Therapy of Renal Cancer Cells. (Pubmed Central) - May 21, 2022
In this study, we analyzed the global expression of B7 immune checkpoint family members (PD-L1, PD-L2, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6, and B7-H7) in human renal cancer cells (Caki-1, A-498, and 786-O cell lines) upon treatment with clinically relevant targeted drugs, including tyrosine kinase inhibitors (Axitinib, Cabozantinib, and Lenvatinib) and mTOR inhibitors (Everolimus and Temsirolimus)...Knocking down the expression of B7-H4 by RNA interference (RNAi) using small interfering RNA (siRNA) decreased renal cancer cell viability and increased drug sensitivity. Our results suggest that B7-H4 expression is induced upon targeted therapy in renal cancer cells and highlight B7-H4 as an actionable immune checkpoint protein in combination with targeted therapy in advanced renal cancer cases resistant to current treatments.
- |||||||||| Farydak (panobinostat) / Secura Bio, Torisel (temsirolimus) / Pfizer
Biomarker, Clinical data, Journal, Tumor Mutational Burden, Tumor microenvironment, IO biomarker, Epigenetic controller: Identification of Tumor Microenvironment and DNA Methylation-Related Prognostic Signature for Predicting Clinical Outcomes and Therapeutic Responses in Cervical Cancer. (Pubmed Central) - May 7, 2022
Finally, four drugs (panobinostat, lenvatinib, everolimus, and temsirolimus) were found to have potential therapeutic implications for patients with a high-risk score. Our findings highlight that the TME and DNA methylation-related prognostic signature can accurately predict the prognosis of CC and may be important for stratified management of patients and precision targeted therapy.
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Systemic Therapy for Chondrosarcoma. (Pubmed Central) - Apr 30, 2022
Conventional CS is inherently resistant to cytotoxic chemotherapy and patients may benefit from antiangiogenic therapy including off-label use of pazopanib...Upon progression and with functional status permitting, alternative options include mTOR inhibitors (sirolimus, temsirolimus) or other tyrosine kinase inhibitors (dasatinib), though no clear sequencing data exists...Alternative treatment options include immunotherapy with pembrolizumab or ivosidenib in IDH1-mutant, dedifferentiated CS, but questionable efficacy was observed in small sample sizes with either approach. In mesenchymal CS, treatment with Ewing sarcoma-like chemotherapy regimens may be considered, although data supporting its use is even more limited given its rarity.
- |||||||||| Recentin (cediranib) / AstraZeneca, Torisel (temsirolimus) / Pfizer
P1 data, Clinical Trial,Phase I, Journal: A phase I study of AZD2171 and Temsirolimus in patients with advanced gynecological malignancies. (Pubmed Central) - Apr 29, 2022
Despite a conservative dose escalation, the toxicity data demonstrated that the combination of AZD2171 and Temsirolimus was not tolerable. Increased awareness of novel toxicities, pharmacological interactions, coupled with strict patient selection and early mitigation of side effects may enhance phase I clinical trial development.
- |||||||||| Avastin (bevacizumab) / Roche, Torisel (temsirolimus) / Pfizer
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer (clinicaltrials.gov) - Apr 27, 2022
P1, N=278, Active, not recruiting,
Based on the emerging biomarker results, a tissue-agnostic study in patients with TSC1 and TSC2 alterations has been initiated (NCT05103358). Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono, Torisel (temsirolimus) / Pfizer
Review, Journal: Therapeutic approaches for the treatment of head and neck squamous cell carcinoma-An update on clinical trials. (Pubmed Central) - Apr 24, 2022
Various monoclonal antibodies, such as cetuximab and bevacizumab, which target the EGFR and VEGFR, respectively, as well as other signaling pathway inhibitors, such as temsirolimus and rapamycin, are also being studied for the treatment of HNSCC. We have reviewed the primary targets in active clinical studies in this study, with a particular focus on the medications and drug targets used.
- |||||||||| 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.
- |||||||||| 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.
- |||||||||| Torisel (temsirolimus) / Pfizer
GERM CELL TUMOR WITH MALIGNANT TRANSFORMATION () - Apr 20, 2022 - Abstract #ASPHO2022ASPHO_194;
Teratomas with malignant transformation are mainly observed in post-pubertal males. Malignant somatic transformation in and of itself is rare occurring in 3 to 8 percent of all pediatric and adult metastatic germ cell tumors combined.
- |||||||||| 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.
- |||||||||| Journal: Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer. (Pubmed Central) - Apr 19, 2022
Moreover, our results showed patients in C1 NSCLC had the highest sensitivity to AKT.inhibitor, AZD6482 (PI3K inhibitor)...To better predict the prognosis of NSCLC, we analyzed the correlation between stress granule regulator expression and overall survival time in NSCLC and constructed a Stress Granule Score including EIF2S1, CTSG, EIF4G1, IGF2BP1, PABPC1 to predict the prognosis of NSCLC. Overall, this study for the first time uncovers the effect of stress particles on drug response, immune response, and prognosis, laying a new theoretical foundation for the NSCLC prognosis and treatment.
- |||||||||| 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.
- |||||||||| niclosamide / Generic mfg.
Journal: Repurposing of antiparasitic niclosamide to inhibit respiratory syncytial virus (RSV) replication. (Pubmed Central) - Apr 12, 2022
Although a disruption of the mechanistic target of rapamycin complex 1 (mTORC1) pathway by niclosamide was previously hypothesized as a mechanism against pH-independent viruses like RSV, using a chemical mTORC1 inhibitor, temsirolimus, and a chemical mTORC1 agonist, MHY1485 (MHY), we show here that the mechanism of RSV inhibition by niclosamide was mTORC1 independent. Indeed, our data indicated that niclosamide hindered RSV infection via proapoptotic activity by a reduction of AKT prosurvival protein, activation of cleaved caspase-3 and PARP (poly ADP-ribose polymerase), and an early apoptosis induction.
- |||||||||| FDA event, Review, Journal: Properties of FDA-approved small molecule protein kinase inhibitors: a 2022 update. (Pubmed Central) - Apr 8, 2022
All of the FDA-approved drugs are orally effective with the exception of netarsudil, temsirolimus, and the newly approved trilaciclib. This review summarizes the physicochemical properties of all 68 FDA-approved small molecule protein kinase inhibitors including lipophilic efficiency and ligand efficiency.
- |||||||||| Avastin (bevacizumab) / Roche
P2 data, Clinical Trial,Phase II, Journal, Monotherapy: Phase II Trial of Bevacizumab Monotherapy in Pancreatic Neuroendocrine Tumors. (Pubmed Central) - Mar 23, 2022
Bevacizumab demonstrated promising antitumor activity in progressive PNETs comparable to standard targeted therapy. Although this study failed to reject the null hypothesis (RR, 10%), bevacizumab seems a reasonable monotherapy and a potential component of combination therapies given clinical activity and low rates of adverse events.
- |||||||||| Torisel (temsirolimus) / Pfizer, Sutent (sunitinib) / Pfizer
Trial completion date, Metastases: A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours (clinicaltrials.gov) - Mar 21, 2022
P2, N=137, Active, not recruiting,
Although this study failed to reject the null hypothesis (RR, 10%), bevacizumab seems a reasonable monotherapy and a potential component of combination therapies given clinical activity and low rates of adverse events. Trial completion date: Dec 2021 --> Sep 2022
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Structural mechanism of allosteric activation of TRPML1 by PI(3,5)P and rapamycin. (Pubmed Central) - Mar 11, 2022
To reveal the structural basis underlying the synergistic activation of TRPML1 by PI(3,5)P and rapamycin, we determined the high-resolution cryoelectron microscopy (cryo-EM) structures of the mouse TRPML1 channel in various states, including apo closed, PI(3,5)P-bound closed, and PI(3,5)P/temsirolimus (a rapamycin analog)-bound open states. These structures, combined with electrophysiology, elucidate the molecular details of ligand binding and provide structural insight into how the TRPML1 channel integrates two distantly bound ligand stimuli and facilitates channel opening.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Cost Effectiveness of Cabozantinib Plus Nivolumab As First-Line Treatment for Renal Cell Carcinoma () - Mar 8, 2022 - Abstract #ISPOR2022ISPOR_3;
P3
Under a lifetime horizon (50-years), patients entered the model in the progression-free state and received 1L CaboNivo or an alternative tyrosine kinase inhibitor (TKI; cabozantinib, pazopanib, temsirolimus, tivozanib, sorafenib, sunitinib) or combination (axitinib/avelumab, axitinib/pembrolizumab, ipilimumab/nivolumab, lenvatinib/pembrolizumab)... CaboNivo had a favourable cost-effectiveness profile compared to other globally available 1L treatment options when using French costs over a lifetime horizon.
- |||||||||| cladribine / Generic mfg., lenalidomide / Generic mfg.
Journal: Mantle cell lymphoma management trends and novel agents: where are we going? (Pubmed Central) - Mar 4, 2022
Epigenetic agents (e.g. cladribine and vorinostat), mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus and everolimus), and monoclonal antibodies and/or antibody-drug conjugates (e.g. obinutuzumab, polatuzumab, and ublituximab) are promising therapeutic agents currently under clinical trial investigation...However, due to its intricate pathology nature and high relapse incidence, there are still unmet needs in developing optimal therapeutic strategies for both frontline and relapsed/refractory settings. The ultimate goal is to develop innovative personalized combination therapy approaches for the purpose of delivering precision medicine to cure this disease.
- |||||||||| Torisel (temsirolimus) / Pfizer, Sutent (sunitinib) / Pfizer
Trial completion date, Trial primary completion date, Metastases: Phase II Study of Alternating Sunitinib and Temsirolimus (clinicaltrials.gov) - Feb 21, 2022
P2, N=37, Active, not recruiting,
The ultimate goal is to develop innovative personalized combination therapy approaches for the purpose of delivering precision medicine to cure this disease. Trial completion date: Dec 2021 --> Jun 2022 | Trial primary completion date: Dec 2021 --> Jun 2022
- |||||||||| 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.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Biomarker, Review, Journal: New frontiers against sorafenib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers. (Pubmed Central) - Feb 10, 2022
Herein, we comprehensively summarize the underlying mechanisms of sorafenib resistance and molecular biomarkers for predicting sorafenib responsiveness. Moreover, we outline strategies suitable for overcoming sorafenib resistance and prospect potential approaches for identifying biomarkers associated with sorafenib resistance in RCC, which contributes to guide individualized and precision drug therapy.
- |||||||||| 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.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal, PD(L)-1 Biomarker, IO biomarker: Helicobacter urease suppresses cytotoxic CD8 + T cell responses through activating Myh9-dependent induction of PD-L1. (Pubmed Central) - Feb 4, 2022
Furthermore, blocking mTORC1 activation with its inhibitor Temsirolimus reversed UreB-induced PD-L1 upregulation and the subsequently inhibitory effects of BMDMs on activation of cytotoxic CD8 + T cell responses. Overall, our data unveil a novel immunosuppressive mechanism of UreB during H. pylori infection, which may provide valuable clue for the optimization of H. pylori vaccine.
- |||||||||| 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.
- |||||||||| 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.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono, Torisel (temsirolimus) / Pfizer
Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases: Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease (clinicaltrials.gov) - Jan 20, 2022
P1, N=155, Active, not recruiting,
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. Recruiting --> Active, not recruiting | Trial completion date: Mar 2021 --> Mar 2022 | Trial primary completion date: Mar 2020 --> Mar 2022
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