- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Review, Journal: Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review. (Pubmed Central) - Apr 8, 2024
Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy...These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes...Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications.
- |||||||||| MK-0752 / Merck (MSD)
Journal: Effect of Notch Signal Pathway on Steroid Synthesis Enzymes in TM3 Cells. (Pubmed Central) - Apr 28, 2023
MK-0752 and overexpression of different Notch members had no influence on the expression of GATA4 and GATA6. In conclusion, Notch1 signaling may contribute to the steroid synthesis in Leydig cells through regulating SF1 and downstream steroidogenic enzymes (3?-HSD, StAR and P450Scc).
- |||||||||| MK-0752 / Merck (MSD)
Increasing DAXX expression in ER+ breast cancer cells to overcome endocrine therapy resistance (Hall 1) - Oct 10, 2022 - Abstract #SABCS2022SABCS_943;
The mechanism by which DAXX inhibits ET-resistant BC is through activation of JNK signaling, regulation of pro-apoptotic genes, and induction of apoptosis. The translational impact of this research is to identify novel agents that can increase DAXX expression and test them pre-clinically and in clinical trials for patients with ET-resistant breast cancer.
- |||||||||| MK-0752 / Merck (MSD), RG4733 / Roche, LY-411575 / Eli Lilly
Review, Journal: DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment. (Pubmed Central) - Dec 13, 2021
The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, DLL4 mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.
- |||||||||| MK-0752 / Merck (MSD), volasertib (BI 6727) / Oncoheroes
Journal: PLK1 and NOTCH Positively Correlate in Melanoma and their Combined Inhibition Results in Synergistic Modulations of Key Melanoma Pathways. (Pubmed Central) - Aug 14, 2021
We identified the modulations of several key genes relevant to melanoma progression/metastasis, including MAPK, PI3K, and RAS, as well as some new genes such as Apobec3G, BTK and FCER1G which have not been well-studied in melanoma. In conclusion, our study demonstrated a synergistic anti-proliferative response of a concomitant targeting of PLK1 and NOTCH in melanoma, unraveling a potential novel therapeutic approach for detailed preclinical/clinical evaluation.
- |||||||||| MK-0752 / Merck (MSD), volasertib (BI 6727) / Oncoheroes
RNA-seq analysis of differential gene expression in melanoma cells after combined inhibition of Plk1 and Notch (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_3214;
Overall, our data demonstrated that not only does targeting both Plk1 and Notch1 signaling pathways alters multiple melanoma progression pathways, but it may also potentially result in an increased sensitivity to other therapeutic targets, such as immune checkpoint blockade. However, these mechanistic findings need to be validated further in other relevant in vitro and in vivo models.
- |||||||||| MK-0752 / Merck (MSD)
Trial completion, Phase classification, Combination therapy, Surgery: Study Of MK-0752 In Combination With Tamoxifen Or Letrozole to Treat Early Stage Breast Cancer (clinicaltrials.gov) - Sep 4, 2019
P4, N=22, Completed,
These findings suggest that the cross-talk between Notch1 signaling and CXCL12/CXCR4 system could contribute to the self-renewal and invasion of GICs, and this discovery could help drive the design of more effective therapies in Notch1-targeted treatment of GBMs. Active, not recruiting --> Completed | Phase classification: PN/A --> P4
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma
Journal: IL6 blockade potentiates the anti-tumor effects of γ-secretase inhibitors in Notch3-expressing breast cancer. (Pubmed Central) - Aug 21, 2019
Furthermore, HIF1α upregulates Notch3 expression via direct binding to the Notch3 promoter and subsequently downregulates BCSCs by decreasing the IL6 levels in Notch3-expressing breast cancer cells. Utilizing both breast cancer cell line xenografts and patient-derived xenografts (PDX), we showed that the combination of MK-0752 and Tocilizumab significantly decreases BCSCs and inhibits tumor growth and thus might serve as a novel therapeutic strategy for treating women with Notch3-expressing breast cancers.Cell Death and Differentiation advance online publication, 13 October 2017; doi:10.1038/cdd.2017.162.
- |||||||||| MK-0752 / Merck (MSD)
Journal, BRCA Biomarker: Minigene Splicing Assays Identify 12 Spliceogenic Variants of BRCA2 Exons 14 and 15. (Pubmed Central) - Jun 14, 2019
...Thus, according to the guidelines of the American College of Medical Genetics and Genomics, eight variants should be classified as pathogenic (c.7008-2A > T, c.7008-1G > A, c.7435+1G > C, c.7436-2A > T, c.7436-2A > G, c.7617+1G > A, c.7617+1G > T, and c.7617+2T > G), one as likely pathogenic (c.7008-3C > G) and three remain as variants of uncertain clinical significance or VUS (c.7177A > G, c.7447A > G and c.7501C > T)...While bioinformatics predictions of splice site variants were accurate, those of enhancer or silencer variants were poor (only 3/23 spliceogenic variants) which showed weak impacts on splicing (∼5-16% of aberrant isoforms). So, the Exonic Splicing Enhancer and Silencer (ESE and ESS, respectively) prediction algorithms require further improvement.
- |||||||||| MK-0752 / Merck (MSD)
Trial primary completion date, Combination therapy, Surgery: Study Of MK-0752 In Combination With Tamoxifen Or Letrozole to Treat Early Stage Breast Cancer (clinicaltrials.gov) - Apr 15, 2015
P=N/A, N=22, Active, not recruiting,
Gemcitabine and a γ-secretase inhibitor (MK-0752) can be combined at their full, single-agent RP2Ds.British Journal of Cancer advance online publication, 13 February 2018; doi:10.1038/bjc.2017.495 www.bjcancer.com. Trial primary completion date: Aug 2011 --> May 2015
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