- |||||||||| Caprelsa (vandetanib) / Sanofi
Journal: Repurposing vandetanib plus everolimus for the treatment of ACVR1-mutant diffuse intrinsic pontine glioma. (Pubmed Central) - Mar 15, 2022 This combination is well-tolerated in vivo, and significantly extended survival and reduced tumor burden in an orthotopic ACVR1-mutant patient-derived DIPG xenograft model. Four patients with ACVR1-mutant DIPG were treated with vandetanib plus mTOR inhibitor, informing the dosing and toxicity profile of this combination for future clinical studies.
- |||||||||| vistusertib (AZD2014) / AstraZeneca
Review, Journal: mTOR Signaling and Potential Therapeutic Targeting in Meningioma. (Pubmed Central) - Mar 15, 2022 mTOR contributes to redox homeostasis, a vital component of neoplasia. Recent clinical trials have investigated novel chemotherapeutic agents for mTOR inhibition, showing promising results in resistant or recurrent meningiomas.
- |||||||||| Sutent (sunitinib) / Pfizer
Antisecretory effect of oral targeted therapies in advanced functioning neuroendocrine tumors (the ASSET-NET study) () - Mar 14, 2022 - Abstract #ENETS2022ENETS_307; Introduction: Oral targeted therapies (TTs),everolimus and sunitinib,have demonstrated antitumor activity in patients with advanced progressive neuroendocrine tumors (NETs). Clinical response was achieved in 42.5% of patients treated by TT for advanced progressive NET with uncontrolled clinical secretory syndrome, especially in patients with midgut NETs and in those with VIPomas receiving sunitinib.
- |||||||||| everolimus / Generic mfg.
Role of Radiomics in the Everolimus response prediction of metastatic neuroendocrine tumors () - Mar 14, 2022 - Abstract #ENETS2022ENETS_260; In this large clinical practice series, therapy with 177Lu-DOTATATE (PRRT) was safe, with survival data comparable to those shown in clinical trials. Radiomics could be a non-invasive Imaging biomarker with supportive role in clinical management and prediction prognosis of metastatic NETs, that could benefit of target therapy.
- |||||||||| cabergoline / Generic mfg., everolimus / Generic mfg.
DRD2 agonist cabergoline abolished the escape mechanism induced by mTOR inhibitor everolimus in pituitary neuroendocrine tumoral cells () - Mar 14, 2022 - Abstract #ENETS2022ENETS_194; Radiomics could be a non-invasive Imaging biomarker with supportive role in clinical management and prediction prognosis of metastatic NETs, that could benefit of target therapy. These results unveiled that cabergoline overcomes the everolimus escape mechanism in NF-PitNETs and MMQ cells inhibiting p-AKT, paving the way for a potential role of β-arrestin2 as a biomarker predicting PitNETs responsiveness to combined therapy with dopamine agonists.
- |||||||||| everolimus / Generic mfg.
Clinical, Review, Journal: An overview of the efficacy and safety of everolimus in adult solid organ transplant recipients. (Pubmed Central) - Mar 11, 2022 With demonstrated potential to facilitate the reduction of CNI therapy and preserve renal function, everolimus is an alternative to the current standard-of-care CNI-based regimens used in de novo and maintenance solid organ transplantation recipients. Here, we provide an overview of the evidence from the everolimus clinical study program across kidney, liver, heart, and lung transplants, as well as other key data associated with its use in CNI reduction strategies in adult transplant recipients.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Biomarker, Journal, IO biomarker: Longitudinal monitoring of mRNA levels of regulatory T cell biomarkers by using non-invasive strategies to predict outcome in renal transplantation. (Pubmed Central) - Mar 11, 2022 Nevertheless, the safety and efficacy of ICI in solid organ transplant recipients (SOTR) are unclear, since SOTR are usually excluded from clinical investigations due to their high risk for irreversible allograft rejection.. mRNA levels of Treg-associated genes, mainly for solCTLA-4, in peripheral blood could put forward as candidate non-invasive biomarkers of cellular and humoral alloreactivity in clinical transplantation and might help shape immunosuppression, tailor monitoring and achieve better long-term outcomes of kidney transplantation in the wake of "precision medicine".
- |||||||||| everolimus / Generic mfg.
Journal: Unintentional Dual Benefit: Improvement in Secondary Polycythemia in a Patient Receiving Chemotherapy for Metastatic Clear Cell Renal Cell Carcinoma. (Pubmed Central) - Mar 11, 2022 Combining the expression levels of FCER1G and macrophage biomarker CD68 may be a promising postoperative prognostic index for patients with ccRCC. Haemoglobin and haematocrit levels should be closely monitored in renal cell carcinoma (RCC) patients as they may develop secondary polycythemia as a result of their malignancy.Secondary polycythemia can be managed with chemotherapy and immunotherapy in RCC, with anti-cancer agents preventing the need for phlebotomy.Chemotherapy may benefit RCC patients by decreasing tumour burden, preventing progression, and by lowering haemoglobin levels, thus improving secondary polycythemia.
- |||||||||| polyTregs / National Institute of Allergy and Infectious Diseases
Enrollment change, Trial completion date, Trial primary completion date: TASK: Treg Therapy in Subclinical Inflammation in Kidney Transplantation (clinicaltrials.gov) - Mar 10, 2022 P1/2, N=14, Recruiting, In the paper, the progress in this area, as well as the controversies/uncertainties, are reviewed. N=30 --> 14 | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023
- |||||||||| everolimus / Generic mfg.
Using copper chelating agents to simultaneously target epigenetic mechanisms and receptor tyrosine kinase (RTK) signaling in diffuse intrinsic pontine glioma (DIPG) (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_7265; Cytotoxicity assays using copper chelator tetraethylenepentamine (TEPA) demonstrated millimolar efficacy and synergized with mTOR inhibitor everolimus in a panel of DIPG cell lines, with H3-K27M mutant cell lines found to be more sensitive...In vivo investigations demonstrated TEPA’s ability to improve survival in an orthotopic xenograft model, and via xenogen luminescence imaging complete tumor regression in 25% of treated mice. This study indicates copper directly impacts epigenetic and RTK mechanisms, and that their targeting through copper chelation agents represents a potential therapeutic strategy for DIPG, both as a single agent and in combination.
- |||||||||| everolimus / Generic mfg.
Everolimus inhibits angiogenesis and lymphangiogenesis to affect tumor growth in TP53 mutant HNSCC (Section 14) - Mar 9, 2022 - Abstract #AACR2022AACR_5710; Protein and mRNA levels of HIF-1α, VEGF-A, and VEGF-C were downregulated by everolimus treatment in both HMEC-1 and HMEC-1A cell lines. Taken together, our data suggest that everolimus prevents angiogenesis and lymphangiogenesis through the inhibition of HIF-1α, indicating a promising role for mTOR inhibitors in treating HPV-negative TP53 mutant HNSCC patients at high risk for recurrence.
- |||||||||| everolimus / Generic mfg.
Targeting the mTOR pathway for the prevention of er-negative breast cancer (Section 1) - Mar 9, 2022 - Abstract #AACR2022AACR_3607; Our results suggest that everolimus is a promising cancer preventive drug for ER-negative tumors, and that further studies of everolimus in combination with other targeted therapies are warranted. In the future, clinical trials of the everolimus should be considered for the prevention of breast cancer in high-risk patients.
- |||||||||| VS-6766 / Verastem
Rational combinations with the dual RAF/MEK inhibitor VS-6766 for treatment of cutaneous melanoma harboring BRAF, NRAS, NF1 or CRAF mutations (Section 27) - Mar 9, 2022 - Abstract #AACR2022AACR_3591; Clinical responses were also observed with VS-6766 in combination with the focal adhesion kinase (FAK) inhibitor defactinib in patients with low-grade serous ovarian cancer and KRAS mutant NSCLC...In BRAFV600E melanoma cell lines, combination of VS-6766 with BRAFi (encorafenib, vemurafenib, dabrafenib) showed greater synergy than combination of MEKi (binimetinib, cobimetinib, trametinib) with BRAFi...Because CDK4/6 pathway activation has been correlated with poor progression-free survival in melanoma patients treated with BRAFi combined with MEKi, we tested the combination of VS-6766 with the CDK4/6 inhibitor abemaciclib...These preclinical data support clinical testing of VS-6766 in rational combinations for treatment of cutaneous melanoma with BRAF, NRAS, NF1 or CRAF mutations. In clinical trials, a recommended phase 2 dose has been defined for the combination of VS-6766 with everolimus.
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