- |||||||||| Sandostatin LAR Depot (octreotide acetate) / Novartis
Trial completion date, Trial primary completion date, Combination therapy, Metastases: MetNET1: Activity and Safety of Everolimus+Octreotide LAR+Metformin in Advanced Pancreatic Well-differentiated NETs (clinicaltrials.gov) - Jun 10, 2021
P2, N=43, Recruiting,
At 24 months, our study found that patients with predominantly advanced infra-popliteal PAD who were treated with Absorb bioresorbable vascular scaffold reported improved clinical status and a low and durable rate of clinically driven target vessel failure extending out to 24 months. Trial completion date: Jun 2017 --> Jun 2021 | Trial primary completion date: Jun 2017 --> Jun 2021
- |||||||||| everolimus / Generic mfg., capecitabine / Generic mfg.
Journal: Management of Locally Advanced and Unresectable Small Bowel Neuroendocrine Tumours. (Pubmed Central) - Jun 9, 2021
Non-operative management should emphasize symptomatic treatment with somatostatin analogs, nutritional advice and support and palliative care. Successful neoadjuvant approaches utilizing peptide radionucleide receptor therapy and systemic chemotherapy with everolimus or temazolamide/capecitabine have not been reported.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Journal: Impact of Immunosuppressive Strategies on Post-Kidney Transplantation Thrombocytopenia. (Pubmed Central) - Jun 9, 2021
Successful neoadjuvant approaches utilizing peptide radionucleide receptor therapy and systemic chemotherapy with everolimus or temazolamide/capecitabine have not been reported. GRA associated with EVR led to more frequent and severe thrombocytopenia, although we found no significant clinical consequences.
- |||||||||| everolimus / Generic mfg.
Clinical, Review, Journal: Everolimus in kidney transplant recipients at high cardiovascular risk: a narrative review. (Pubmed Central) - Jun 8, 2021
To this end, a panel of Italian experts in the field of transplantation was convened in a series of meetings to assess the current literature on the potential of the mTOR inhibitor everolimus as a cardioprotective agent. This narrative review summarizes the panel's round-table discussions and provides recommendations for CV risk management in KTRs.
- |||||||||| everolimus / Generic mfg., exemestane / Generic mfg.
Clinical, P3 data, Journal, Adverse events: Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population. (Pubmed Central) - Jun 4, 2021
Everolimus plus exemestane is a well-known therapeutic option for aromatase inhibitor pretreated advanced breast cancer patients, and its toxicity profile is similar to that described in previous studies. Close monitoring, especially within the first three months, early intervention with preventive measures and patient education to help recognize the first signs and symptoms of AEs, will help to reduce their incidence and severity.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Preclinical, Journal: Combinatorial Therapies to Overcome BRAF/MEK Inhibitors Resistance in Melanoma Cells: An in vitro Study. (Pubmed Central) - Jun 4, 2021
Our results suggest that the combination of MAPK pathway inhibitors with mTOR pathway inhibitors and DCA should be considered as therapeutic options to treat melanoma patients, as the combinations potentiated the effects of each drug alone. In a cell line resistant to vemurafenib, we verified that combined MAPK inhibitors with inhibition of mTOR pathway and/or DCA metabolism modulation might constitute possible strategies in order to overcome resistance to MAPK inhibition.
- |||||||||| omipalisib (GSK2126458) / GSK
Journal: The PI3K/mTOR dual inhibitor GSK458 potently impedes ovarian cancer tumorigenesis and metastasis. (Pubmed Central) - Jun 3, 2021
In a cell line resistant to vemurafenib, we verified that combined MAPK inhibitors with inhibition of mTOR pathway and/or DCA metabolism modulation might constitute possible strategies in order to overcome resistance to MAPK inhibition. Based on our results, we conclude that GSK458 may serve as an attractive candidate to treat ovarian cancer.
- |||||||||| verapamil / Generic mfg., everolimus / Generic mfg.
Journal, IO biomarker: Follicle inhibition at the primordial stage without increasing apoptosis, with a combination of everolimus, verapamil. (Pubmed Central) - Jun 3, 2021
This decrease was reversed in the presence of FSH after stopping drug administration. The expression of the anti-apoptotic molecule Bcl2 as well as of LC3-II and ATG12 was increased after removal of the Everolimus plus Verapamil combination, indicating reduced apoptosis and increased autophagy, whereas the levels of the proliferation marker PCNA in the granulosa cells were elevated, consistent with initiation of follicular growth.Thus, the combination of Everolimus plus Verapamil is capable of increasing the number of competent primordial follicles while reducing atresia.
- |||||||||| vigabatrin / Generic mfg., everolimus / Generic mfg.
Clinical, Journal: Forehead plaque in a child with epilepsy: A clue for tuberous sclerosis. (Pubmed Central) - Jun 3, 2021
We describe a 10-year-old girl with generalised tonic-clonic seizures whose diagnosis of tuberous sclerosis complex was made in view of the presence of a forehead plaque. Certain clinical pointers such as ashleaf macules, café-au-lait spots, shagreen patches and forehead plaques must therefore be looked for in a child with unprovoked seizures.
- |||||||||| temozolomide / Generic mfg.
Review, Journal: Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions. (Pubmed Central) - Jun 3, 2021
Targeted therapies, such as sunitinib and everolimus, have also shown some positive therapeutic efficacy in small samples of patients...More data will come with future work now focusing on this specific subgroup. The aim of this review is to summarize the current data on digestive NET G-3 and explore future directions for their management.
- |||||||||| [VIRTUAL] Fibroblast-induced paradoxical PI3K pathway activation in colorectal cancer: Role of PTEN and potential implications for PI3K/mTOR inhibition () - Jun 1, 2021 - Abstract #ESMOGI2021ESMO_GI_408;
Methods Sensitivity of cell lines to single (alpelisib, everolimus, MK-2206) and double PI3K/mTOR (gedatolisib and dactolisib) pathway inhibitors was investigated using Crystal Violet assay under differing culture conditions (wo FBS, in the presence of fibroblast-conditioned medium -CM- or in direct co-culture)...Results Based on results obtained in PTEN isogenic cell lines (HCT116 Parental and HCT116 PTEN-/-) under different culture conditions, we show that sensitivity to MEK inhibition (trametinib) is dictated mainly by the genetic background of the cancer cells; conversely, the effect of PI3K/mTOR double inhibition is profoundly influenced by exposure to fibroblast CM...Paradoxical PI3K activation involves the assembly and cellular relocalization of macromolecular complexes orchestrated by the PDZ domain of PTEN, resulting in activation of the mTORC1/p70S6K pathway. Therefore, TME-mediated pathway modulation could be potentially exploited to improve the treatment of PTEN-competent CRC patients and overcome therapeutic resistance to PI3K/mTOR inhibitor.
- |||||||||| everolimus / Generic mfg.
[VIRTUAL] Pancreatic neuroendocrine neoplasia: Experience of a comprehensive cancer center () - Jun 1, 2021 - Abstract #ESMOGI2021ESMO_GI_360;
Globally, 60 (61.9%) surgical procedures were performed, 22 (22.9%) transarterial embolization, 5 (5.2%) other locoregional therapies, 56 (57.7%) somatostatin analogues, 23 (23.7%) Peptide Receptor Radionuclide Therapy, 11 (11.3%) everolimus and 32 (33.0%) chemotherapy...Therapeutic strategies in PAN-NENs are highly diversified and adapted to histological differentiation, stage, hormone hypersecretory-related symptoms and patients characteristics and preferences. NEC and metastatic disease were associated with a significant increase risk of death.
- |||||||||| everolimus / Generic mfg.
Journal: Selective inhibition of mTORC1 in tumor vessels increases antitumor immunity. (Pubmed Central) - Jun 1, 2021
Here we show that low-dose RAD001/everolimus, an mTORC1 inhibitor, selectively targets mTORC1 signaling in endothelial cells (ECs) without affecting tumor cells or immune cells, resulting in tumor vessel normalization and increased antitumor immunity...Importantly, analyses of human tumor data sets support our animal studies. Collectively, these findings demonstrate that endothelial mTORC1 is an actionable target for tumor vessel normalization, which could be leveraged to enhance antitumor immune therapies.
- |||||||||| metformin / Generic mfg., everolimus / Generic mfg.
Journal: Pharmacological inhibition of mTORC1 increases CCKBR-specific tumor uptake of radiolabeled minigastrin analogue [Lu]Lu-PP-F11N. (Pubmed Central) - Jun 1, 2021
No significant difference in the tumor vascularization was observed after five-day RAD001 or metformin treatment. Our data demonstrates, that increased CCKBR protein level by RAD001 pretreatment has the potential to improve tumor uptake of [Lu]Lu-PP-F11N and provides proof-of-concept for the development of molecular strategies aimed at enhancing the level of the targeted receptor, to increase the efficacy of PRRT and nuclear imaging.
- |||||||||| sirolimus / Generic mfg.
[VIRTUAL] Evidence for a nucleolar involvement in the effect of mTOR inhibitors on cell viability () - May 30, 2021 - Abstract #EACR2021EACR_2023;
Conclusion These results indicate that mTORC2 inhibition must be considered therapeutically, in agreement with the ongoing effort to translate those drugs into clinical practice. Importantly, these results agree with the notion that inhibition of nucleolar function is therapeutically useful and that the mTOR pathways offer possible targets to achieve such inhibition.
- |||||||||| sirolimus / Generic mfg.
[VIRTUAL] Evidence for a nucleolar involvement in the effect of mTOR inhibitors on cell viability () - May 30, 2021 - Abstract #EACR2021EACR_2022;
Conclusion These results indicate that mTORC2 inhibition must be considered therapeutically, in agreement with the ongoing effort to translate those drugs into clinical practice. Importantly, these results agree with the notion that inhibition of nucleolar function is therapeutically useful and that the mTOR pathways offer possible targets to achieve such inhibition.
- |||||||||| sirolimus / Generic mfg.
[VIRTUAL] Evidence for a nucleolar involvement in the effect of mTOR inhibitors on cell viability () - May 30, 2021 - Abstract #EACR2021EACR_2021;
Conclusion These results indicate that mTORC2 inhibition must be considered therapeutically, in agreement with the ongoing effort to translate those drugs into clinical practice. Importantly, these results agree with the notion that inhibition of nucleolar function is therapeutically useful and that the mTOR pathways offer possible targets to achieve such inhibition.
- |||||||||| sirolimus / Generic mfg.
[VIRTUAL] Evidence for a nucleolar involvement in the effect of mTOR inhibitors on cell viability () - May 30, 2021 - Abstract #EACR2021EACR_2020;
Conclusion These results indicate that mTORC2 inhibition must be considered therapeutically, in agreement with the ongoing effort to translate those drugs into clinical practice. Importantly, these results agree with the notion that inhibition of nucleolar function is therapeutically useful and that the mTOR pathways offer possible targets to achieve such inhibition.
- |||||||||| dexamethasone / Generic mfg.
[VIRTUAL] mTORC inhibition decrease G6PD levels and triggers cell death in T-lymphoblastic leukaemia (T-ALL) cells () - May 30, 2021 - Abstract #EACR2021EACR_1751;
In vivo studies of NOD/SCID mice inoculated with PDX from glucocorticoid-refractory T-ALL confirmed that Everolimus overcame Dexamethasone resistance. Conclusion These findings provide insight into the crosstalk between mTORC1 and ROS homeostasis in T-ALL and suggest the combination of glucocorticoids with mTORC1 inhibitors as a therapeutic avenue to target refractory T-ALL.
- |||||||||| dexamethasone / Generic mfg.
[VIRTUAL] mTORC inhibition decrease G6PD levels and triggers cell death in T-lymphoblastic leukaemia (T-ALL) cells () - May 30, 2021 - Abstract #EACR2021EACR_1750;
In vivo studies of NOD/SCID mice inoculated with PDX from glucocorticoid-refractory T-ALL confirmed that Everolimus overcame Dexamethasone resistance. Conclusion These findings provide insight into the crosstalk between mTORC1 and ROS homeostasis in T-ALL and suggest the combination of glucocorticoids with mTORC1 inhibitors as a therapeutic avenue to target refractory T-ALL.
- |||||||||| dexamethasone / Generic mfg.
[VIRTUAL] mTORC inhibition decrease G6PD levels and triggers cell death in T-lymphoblastic leukaemia (T-ALL) cells () - May 30, 2021 - Abstract #EACR2021EACR_1749;
In vivo studies of NOD/SCID mice inoculated with PDX from glucocorticoid-refractory T-ALL confirmed that Everolimus overcame Dexamethasone resistance. Conclusion These findings provide insight into the crosstalk between mTORC1 and ROS homeostasis in T-ALL and suggest the combination of glucocorticoids with mTORC1 inhibitors as a therapeutic avenue to target refractory T-ALL.
- |||||||||| dexamethasone / Generic mfg.
[VIRTUAL] mTORC inhibition decrease G6PD levels and triggers cell death in T-lymphoblastic leukaemia (T-ALL) cells () - May 30, 2021 - Abstract #EACR2021EACR_1748;
In vivo studies of NOD/SCID mice inoculated with PDX from glucocorticoid-refractory T-ALL confirmed that Everolimus overcame Dexamethasone resistance. Conclusion These findings provide insight into the crosstalk between mTORC1 and ROS homeostasis in T-ALL and suggest the combination of glucocorticoids with mTORC1 inhibitors as a therapeutic avenue to target refractory T-ALL.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
[VIRTUAL] B7 immune checkpoint proteins as mediators of resistance to targeted therapy in renal cancer cells () - May 30, 2021 - Abstract #EACR2021EACR_1651;
Material and Methods In this study, we have analyzed the global expression of B7-family members (including PD-L1, PD-L2, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6 and B7-H7) in renal cancer cells upon treatment with clinically relevant targeted therapies, including VEGF inhibitors (Axitinib, Cabozantinib, and Lenvatinib) and mTOR inhibitors (Everolimus and Temsirolimus)...Cell functional assays revealed the potential of specific B7 proteins to mediate intrinsic resistance to targeted therapy in renal cancer cells. Conclusion Our findings highlight novel B7 proteins as actionable immune checkpoint proteins in advanced and metastatic renal cancer cases resistant to current treatments.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
[VIRTUAL] B7 immune checkpoint proteins as mediators of resistance to targeted therapy in renal cancer cells () - May 30, 2021 - Abstract #EACR2021EACR_1650;
Material and Methods In this study, we have analyzed the global expression of B7-family members (including PD-L1, PD-L2, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6 and B7-H7) in renal cancer cells upon treatment with clinically relevant targeted therapies, including VEGF inhibitors (Axitinib, Cabozantinib, and Lenvatinib) and mTOR inhibitors (Everolimus and Temsirolimus)...Cell functional assays revealed the potential of specific B7 proteins to mediate intrinsic resistance to targeted therapy in renal cancer cells. Conclusion Our findings highlight novel B7 proteins as actionable immune checkpoint proteins in advanced and metastatic renal cancer cases resistant to current treatments.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
[VIRTUAL] B7 immune checkpoint proteins as mediators of resistance to targeted therapy in renal cancer cells () - May 30, 2021 - Abstract #EACR2021EACR_1649;
Material and Methods In this study, we have analyzed the global expression of B7-family members (including PD-L1, PD-L2, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6 and B7-H7) in renal cancer cells upon treatment with clinically relevant targeted therapies, including VEGF inhibitors (Axitinib, Cabozantinib, and Lenvatinib) and mTOR inhibitors (Everolimus and Temsirolimus)...Cell functional assays revealed the potential of specific B7 proteins to mediate intrinsic resistance to targeted therapy in renal cancer cells. Conclusion Our findings highlight novel B7 proteins as actionable immune checkpoint proteins in advanced and metastatic renal cancer cases resistant to current treatments.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
[VIRTUAL] B7 immune checkpoint proteins as mediators of resistance to targeted therapy in renal cancer cells () - May 30, 2021 - Abstract #EACR2021EACR_1648;
Material and Methods In this study, we have analyzed the global expression of B7-family members (including PD-L1, PD-L2, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6 and B7-H7) in renal cancer cells upon treatment with clinically relevant targeted therapies, including VEGF inhibitors (Axitinib, Cabozantinib, and Lenvatinib) and mTOR inhibitors (Everolimus and Temsirolimus)...Cell functional assays revealed the potential of specific B7 proteins to mediate intrinsic resistance to targeted therapy in renal cancer cells. Conclusion Our findings highlight novel B7 proteins as actionable immune checkpoint proteins in advanced and metastatic renal cancer cases resistant to current treatments.
- |||||||||| pregabalin / Generic mfg., gabapentin / Generic mfg., carbamazepine / Generic mfg.
Clinical, Review, Journal: Neurocognitive Effects of Antiseizure Medications in Children and Adolescents with Epilepsy. (Pubmed Central) - May 29, 2021
There is limited data for cannabidiol, clobazam, eslicarbazepine acetate, ethosuximide, rufinamide, vigabatrin and zonisamide, although the available evidence suggests these drugs are not associated with severe cognitive impairment. There was too little information to reach conclusions about the effects of brivaracetam, felbamate, gabapentin, pregabalin, retigabine, stiripentol or tiagabine.
- |||||||||| everolimus / Generic mfg.
Preclinical, Journal: Everolimus enhances TRAIL- mediated anti-tumor activity of liver resident natural killer cells in mice. (Pubmed Central) - May 28, 2021
Activated FoxO1 both reduced T-bet expression and induced TRAIL expression, thereby inhibiting NK cell maturation and promoting the antitumor activity of the immature subset of liver NK cells in response to EVR-treatment. These findings indicate that EVR-treatment enhances the antitumor activity of immature liver resident NK cells through TRAIL upregulation.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion date, Trial primary completion date, Metastases: Lenvatinib and Everolimus in Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - May 28, 2021
P1, N=15, Recruiting,
These findings indicate that EVR-treatment enhances the antitumor activity of immature liver resident NK cells through TRAIL upregulation. Trial completion date: Apr 2021 --> Apr 2022 | Trial primary completion date: Apr 2021 --> Apr 2022
|
