- |||||||||| Torisel (temsirolimus) / Pfizer
Journal, Heterogeneity: A Gaussian Mixture-Model Exploiting Pathway Knowledge for Dissecting Cancer Heterogeneity. (Pubmed Central) - Feb 27, 2021 Additionally, we show how this methodology can provide a basis for comparing the killing rate of different drugs for a heterogeneous cancer tissue. This obviously has important implications for designing efficient drugs for treating heterogeneous malignant tumors.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Network determinants of cardiovascular calcification and repositioned drug treatments. (Pubmed Central) - Feb 26, 2021 An integrated network analytical approach identified novel mediators of ectopic cardiovascular calcification and biologically plausible candidate drugs that could be repurposed to target calcification. This methodological framework for drug repurposing has broad applicability to other diseases.
- |||||||||| Sylvant (siltuximab) / Jazz, trebananib (AMG 386) / Amgen, Torisel (temsirolimus) / Pfizer
Biomarker, Enrollment closed, Trial primary completion date: Identification of Molecular Biomarkers for Cancer Target Therapy Efficacy (clinicaltrials.gov) - Feb 25, 2021 P=N/A, N=200, Active, not recruiting, This methodological framework for drug repurposing has broad applicability to other diseases. Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2020 --> Apr 2021
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination. (Pubmed Central) - Feb 13, 2021 The combination of conditional knockout mouse models and viral vector-mediated autophagy-modulating strategies in vivo showed that cannabinoid CB receptors located on neurons belonging to the direct (striatonigral) pathway are required for the motor-impairing activity of Δ-tetrahydrocannabinol by inhibiting local autophagy. Taken together, these findings identify inhibition of autophagy as an unprecedented mechanistic link between cannabinoids and motor performance, and suggest that activators of autophagy might be considered as potential therapeutic tools to treat specific cannabinoid-evoked behavioral alterations.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: KLF4-mutated meningiomas show enhanced hypoxia signaling and respond to mTORC1 inhibitor treatment. (Pubmed Central) - Jan 16, 2021 Finally, we demonstrate that KLF4 mutated tumors are susceptible to mTOR inhibition by Temsirolimus. Taken together, our data link the KLF4 mediated upregulation of HIF pathways to the clinical and biological characteristics of these skull base meningiomas possibly opening new therapeutic avenues for this distinct meningioma subtype.
- |||||||||| Torisel (temsirolimus) / Pfizer
Clinical, Journal: Mutations and Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma. (Pubmed Central) - Jan 13, 2021 Tumors from 58 patients from the phase III trial of temsirolimus and 51 local patients with mRCC treated with rapalogs were studied...In addition, none of the 6 genes commonly mutated in RCC showed a mutation pattern that correlated with CB. Overall, in this large and diverse population of mRCC patients, there is no suggestion of correlation between response to rapalog therapy and mutation status for mTOR pathway genes.
- |||||||||| FDA event, Review, Journal: Properties of FDA-approved small molecule protein kinase inhibitors: a 2020 update. (Pubmed Central) - Jan 6, 2021
More than half of the antagonists (29) have lipophilic efficiency values of less than five while the recommended optima range from 5-10. One of the troublesome problems with both targeted and cytotoxic drugs in the treatment of malignant diseases is the near universal development of resistance to every therapeutic modality.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Cannabinoid-induced motor dysfunction via autophagy inhibition. (Pubmed Central) - Dec 30, 2020 The combination of various genetic strategies in vivo supports the idea that CNR1 molecules located on neurons belonging to the direct (striatonigral) pathway are required for the autophagy- and motor-impairing activity of THC. By identifying autophagy as a mechanistic link between THC and motor performance, our findings may open a new conceptual view on how cannabis acts in the brain.
- |||||||||| Torisel (temsirolimus) / Pfizer, Sutent (sunitinib) / Pfizer
Trial completion date, Metastases: Phase II Study of Alternating Sunitinib and Temsirolimus (clinicaltrials.gov) - Dec 17, 2020 P2, N=37, Active, not recruiting, By identifying autophagy as a mechanistic link between THC and motor performance, our findings may open a new conceptual view on how cannabis acts in the brain. Trial completion date: Dec 2020 --> Jun 2021
- |||||||||| Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Trial completion date, Combination therapy, Metastases: A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886) (clinicaltrials.gov) - Dec 4, 2020 P1, N=140, Active, not recruiting, This powerful model predicts several drugs that should be studied in depth to find new chemotherapy regimens and to propose new strategies for osteosarcoma treatment. Trial completion date: Dec 2020 --> Dec 2021
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: Genetic deletion of S6k1 does not rescue the phenotypic deficits observed in the R6/2 mouse model of Huntington's disease. (Pubmed Central) - Nov 19, 2020 It has been shown that manipulating the mTOR (mammalian target of rapamycin) pathway using rapamycin or its analogue CCI-779 can improve the cellular and behavioural phenotypes of HD models...Additionally, no improvements were seen in brain mass reduction or mutant huntingtin protein aggregate levels. Therefore, these results suggest that while a reduction in S6K1 signalling has beneficial effects on ageing it is unlikely to be a therapeutic strategy for HD patients.
- |||||||||| Revlimid (lenalidomide) / BMS, Torisel (temsirolimus) / Pfizer
[VIRTUAL] Phase I/II Clinical Trial of Temsirolimus and Lenalidomide in Patients with Relapsed and Refractory Lymphomas (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_965; Lenalidomide (LEN) is currently approved for use in indolent non-Hodgkin lymphomas, and has several potential synergistic and overlapping targets with PI3K/mTOR/Akt inhibition...The ORR for HL patients in the other lymphoma cohort, the majority of whom had relapsed after brentuximab vedotin (BV) and autologous stem cell transplantation (ASCT), was 80% (35% CR)...TEM and LEN may be a suitable option for treatment of HL after BV and ASCT, including as a bridge to allogeneic stem cell transplantation. Further study of PI3K/Akt/mTOR inhibition in combination with lenalidomide is warranted, particularly in relapsed HL.
- |||||||||| everolimus / Generic mfg., irinotecan / Generic mfg., bromocriptine / Generic mfg.
Journal: The Route to 'Chemobrain' - Computational probing of neuronal LTP pathway. (Pubmed Central) - Oct 27, 2020 The study identified novel off-target interactions by Dactinomycin, Temsirolimus, and Everolimus against NMDA, AMPA, PKA and ERK2, while Irinotecan, Bromocriptine and Dasatinib were top interacting drugs for CaMKII. This study presents with basic foundational knowledge regarding potential chemotherapeutic interference in LTP pathway which may modulate neurotransmission and synaptic plasticity in patient receiving these chemotherapies.
- |||||||||| Torisel (temsirolimus) / Pfizer
Journal: A Drug Repurposing and Protein-Protein Interaction Network Study of Ribosomopathies Using Yeast as a Model System. (Pubmed Central) - Oct 24, 2020 To support the computational results, an experimental study was conducted using in-house manufactured microfluidic bioreactor platform, while the effect of the drug temsirolimus, Tor1 inhibitor, on yeast cells was investigated by following Nop56 protein expression. In conclusion, these results inform the ways in which ribosomopathies and associated common complex human diseases materialize and how drug repurposing might accelerate therapeutic innovation through bioinformatic studies of yeast.
- |||||||||| Trial completion date, Trial primary completion date, Tumor mutational burden, BRCA Biomarker, MSi-H Biomarker, PARP Biomarker, PD(L)-1 Biomarker, Metastases: TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (clinicaltrials.gov) - Oct 23, 2020
P2, N=3279, Recruiting, In conclusion, these results inform the ways in which ribosomopathies and associated common complex human diseases materialize and how drug repurposing might accelerate therapeutic innovation through bioinformatic studies of yeast. Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2021 --> Dec 2023
- |||||||||| Leustatin (cladribine) / J&J, Opdivo (nivolumab) / Ono Pharma, BMS, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] New drugs for low grade lymphoproliferative diseases (ATİLLA YALÇIN HALL) - Sep 23, 2020 - Abstract #EHOC2020EHOC_28; Tazemetostat a novel EZH2 inhibitor recently received accelerated approval by FDA for patients with RR-FL and EZH2 gene mutations, following the results of a phase-II study...Immune check point inhibitors (Nivolumab, Pemprolizumab, Atezolizumab) are promising as third line treatment and beyond. Other agents under investigation include the inhibitor of nuclear export selinexor, the SYK inhibitor entospletinib, the dual SYK/JAK inhibitor certulatinib and the CDK inhibitors flavopiridol and dinaciclib.
- |||||||||| everolimus / Generic mfg.
Review, Journal: Recent advances in the systemic treatment of metastatic non-clear cell renal cell carcinomas. (Pubmed Central) - Sep 10, 2020 Everolimus, pazopanib, axitinib and nivolmab might also be viable options...Evidence is still lacking regarding the treatment for other rare non-clear cell renal cell carcinomas. Appropriate sequential therapies using antivascular endothelial growth factor therapies, mammalian target of rapamicin inhibitors and immuno-oncology drugs should be established for each non-clear cell renal cell carcinoma.
- |||||||||| 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) - Sep 9, 2020 P2, N=137, Active, not recruiting, Appropriate sequential therapies using antivascular endothelial growth factor therapies, mammalian target of rapamicin inhibitors and immuno-oncology drugs should be established for each non-clear cell renal cell carcinoma. Trial completion date: Jul 2020 --> Dec 2020
- |||||||||| sirolimus / Generic mfg.
Journal: DR5 related autophagy can promote apoptosis in gliomas after irradiation. (Pubmed Central) - Sep 1, 2020 Unlike RAP and CCI779, ABT737 and TMZ were able to increase DR5 expression and further induce cell death. Therefore, we have concluded that DR5 plays a novel and indispensable role in promoting cell apoptosis under irradiation and suggest a potential therapeutic approach for glioblastoma treatment.
- |||||||||| doxorubicin hydrochloride / Generic mfg., cyclophosphamide intravenous / Generic mfg., Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Journal: Mantle cell lymphoma: therapeutic options in transplant-ineligible patients. (Pubmed Central) - Aug 30, 2020 Novel targeted agents now offer more promise than traditional chemotherapy or immunochemotherapy for both previously treated and untreated disease, and should also improve outcomes for older MCL patients. Here, we review standard therapies currently in use and novel agents that may soon be available for MCL patients and particularly for those unsuitable for ASCT.
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