scholarly journals Therapeutic efficacy of liposomal Grb2 antisense oligodeoxynucleotide (L-Grb2) in preclinical models of ovarian and uterine cancer

Oncotarget ◽  
2020 ◽  
Vol 11 (29) ◽  
pp. 2819-2833
Author(s):  
Olivia D. Lara ◽  
Emine Bayraktar ◽  
Paola Amero ◽  
Shaolin Ma ◽  
Cristina Ivan ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Uterine Cancer ◽  
Antisense Oligodeoxynucleotide ◽  
Preclinical Models

scholarly journals MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer

2015 ◽  
Vol 21 (24) ◽  
pp. 5499-5510 ◽  
Author(s):  
Celina García-García ◽  
Martín A. Rivas ◽  
Yasir H. Ibrahim ◽  
María Teresa Calvo ◽  
Albert Gris-Oliver ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Efficacy ◽  
Tp53 Mutation ◽  
Preclinical Models

scholarly journals Repurposing Tin Mesoporphyrin as an Immune Checkpoint Inhibitor Shows Therapeutic Efficacy in Preclinical Models of Cancer

2018 ◽  
Vol 24 (7) ◽  
pp. 1617-1628 ◽  
Author(s):  
Tamara Muliaditan ◽  
James W. Opzoomer ◽  
Jonathan Caron ◽  
Mary Okesola ◽  
Paris Kosti ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Therapeutic Efficacy ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Preclinical Models

scholarly journals Significant Therapeutic Efficacy with Combined Radioimmunotherapy and Cetuximab in Preclinical Models of Colorectal Cancer

2015 ◽  
Vol 56 (8) ◽  
pp. 1239-1245 ◽  
Author(s):  
V. Vassileva ◽  
V. Rajkumar ◽  
M. Mazzantini ◽  
M. Robson ◽  
A. Badar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Efficacy ◽  
Preclinical Models

scholarly journals Mechanistic Basis for In Vivo Therapeutic Efficacy of CK2 Inhibitor CX-4945 in Acute Myeloid Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1127
Author(s):  
Morgann Klink ◽  
Mohammad Atiqur Rahman ◽  
Chunhua Song ◽  
Pavan Kumar Dhanyamraju ◽  
Melanie Ehudin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Dna Binding ◽  
Therapeutic Effect ◽  
Therapeutic Efficacy ◽  
Myeloid Leukemia ◽  
B Cell Lymphoma ◽  
Preclinical Models ◽  
Ck2 Inhibitor ◽  
Acute Myeloid

Protein Kinase CK2 (Casein Kinase 2 or CK2) is a constitutively active serine-threonine kinase overactive in human malignancies. Increased expression and activity of CK2 in Acute Myeloid Leukemia (AML) is associated with a poor outcome. CK2 promotes AML cell survival by impinging on multiple oncogenic signaling pathways. The selective small-molecule CK2 inhibitor CX-4945 has shown in vitro cytotoxicity in AML. Here, we report that CX-4945 has a strong in vivo therapeutic effect in preclinical models of AML. The analysis of genome-wide DNA-binding and gene expression in CX-4945 treated AML cells shows that one mechanism, by which CK2 inhibition exerts a therapeutic effect in AML, involves the revival of IKAROS tumor suppressor function. CK2 phosphorylates IKAROS and disrupts IKAROS’ transcriptional activity by impairing DNA-binding and association with chromatin modifiers. Here, we demonstrate that CK2 inhibition decreases IKAROS phosphorylation and restores IKAROS binding to DNA. Further functional experiments show that IKAROS negatively regulates the transcription of anti-apoptotic genes, including BCL-XL (B cell Lymphoma like–2 like 1, BCL2L1). CX-4945 restitutes the IKAROS-mediated repression of BCL-XL in vivo and sensitizes AML cells to apoptosis. Using CX-4945, alongside the cytotoxic chemotherapeutic drug daunorubicin, augments BCL-XL suppression and AML cell apoptosis. Overall, these results establish the in vivo therapeutic efficacy of CX-4945 in AML preclinical models and determine the role of CK2 and IKAROS in regulating apoptosis in AML. Furthermore, our study provides functional and mechanistic bases for the addition of CK2 inhibitors to AML therapy.

Effect of therapeutic targeting of EMP2 on breast and endometrial cancer stem cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3080-3080
Author(s):  
Madhuri Wadehra ◽  
Meagan Kiyohara ◽  
Negin Ashki ◽  
Ann Chan
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Endometrial Cancer ◽  
Cancer Stem Cells ◽  
Therapeutic Efficacy ◽  
Uterine Cancer ◽  
Breast Cancers ◽  
Novel Target

3080 Background: There is increasing evidence that tumor-initiating cancer stem cells (CSCs) contribute to tumor metastasis and therapeutic resistance. In breast and endometrial cancers, metastatic CSCs are defined as CD44+/CD24- and ALDH+, and in this study, we define another marker epithelial membrane protein-2 (EMP2) as a novel target for this population of cells. EMP2 is an oncogene whose expression has been shown to correlate with tumor progression and survival in a number of human cancers including triple-negative breast, ovarian, and endometrial tumors. Methods: A number of cancer cell lines were utilized both in vitro and in vivo to determine if EMP2 expression levels alter the number and expression of CSC markers. To translate this work, EMP2 and ALDH expression were correlated in primary human endometrial and breast cancers. To determine the therapeutic efficacy of our fully-human EMP2 IgG1 antibody, xenografts from breast or uterine cancer were treated, removed, and then reinjected into secondary mice. Results: In this study, we show new evidence that EMP2 is highly expressed in CSCs. High levels of EMP2 increase the tumor forming potential of both endometrial and breast cancer lines. In tumors created from these cells, high levels of ALDH+ expression were also observed. In contrast, reduction in EMP2 decreased CD44 expression and ALDH activity both in vitro and in vivo, with the net consequence of poorly vascularized and slow growing tumors. We have recently developed a novel monoclonal antibody to EMP2 and have started testing its therapeutic efficacy. In vitro treatment with EMP2 IgG1 reduced HIF-1a, CD44, and ALDH levels, ultimately leading to caspase mediated apoptosis. Treatment of breast cancer cells with EMP2 IgG1 reduced tumor load in both subcutaneous and metastatic models of breast and endometrial cancer resulting in a significant improvement in survival. Reinjection of these cells post treatment into secondary mice failed to efficiently form, and histological examination of the tumors revealed significant necrosis and elimination of ALDH+ CSCs. Conclusions: These results suggest that targeting EMP2 may reduce CSCs and represent an attractive target for further therapeutic development.

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