scholarly journals Compartment-specific activation of PPARγ governs breast cancer tumor growth, via metabolic reprogramming and symbiosis

Cell Cycle ◽  
2013 ◽  
Vol 12 (9) ◽  
pp. 1360-1370 ◽  
Author(s):  
Paola Avena ◽  
Wanda Anselmo ◽  
Chenguang Wang ◽  
Richard G. Pestell ◽  
Rebecca S. Lamb ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Metabolic Reprogramming ◽  
Cancer Tumor

Efficacy of DAN-222, a novel investigational polymeric nanoparticle with topoisomerase I inhibitor, as monotherapy in breast cancer models and when combined with PARP inhibitor.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1081-1081
Author(s):  
Ashley P Wright ◽  
Jodi D Bradley ◽  
Timothy Hagerty ◽  
Emily A Wyatt
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Tumor Cells ◽  
Topoisomerase I ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Topoisomerase I Inhibitor ◽  
Polymeric Nanoparticle ◽  
Cancer Tumor

1081 Background: Patients with BRCA-positive HER2-negative breast cancer benefit from PARP inhibitor therapy, but additional benefit is still desired. PARP inhibition alone does not prevent all mechanisms for repairing damage to DNA such as homologous recombination repair. An attractive combination for treating such patients would be combining a topoisomerase I inhibitor with a PARP inhibitor given the dual mechanism this would provide for DNA damage and inhibited repair, leading to tumor cell death. This combination has been tried in multiple phase 1 studies, but myelotoxicity prevented the combination from being evaluated further. DAN-222 is a novel investigational polymeric nanoparticle conjugated with camptothecin, a topoisomerase I inhibitor, that provides significant accumulation of drug in tumor tissues via the enhanced permeability and retention (EPR) effect and significantly reduced bone marrow exposure compared to native chemotherapy. These observations underscore the potential advantages of DAN-222 alone as well as in combination with other agents such as PARP inhibitors in solid tumors. Here, we report the effects of DAN-222 monotherapy and in combination with a PARP inhibitor on the growth inhibition in an HRD+ TNBC breast cancer (MDA-MB-436) and an HRD- ovarian (OVCAR3) xenograft mouse model. Methods: HRD+ breast cancer tumor cells (MDA-MB-436) were implanted into female NCr nu/nu mice and HRD- ovarian cancer tumor cells (OVCAR3) were implanted into female CB.17 SCID mice. Mice were randomized to vehicle or treatment arms until tumors reached 2000 mm3 or day 45 (MDA-MB-436) or 1000mm3 or day 45 (OVCAR3). The groups evaluated include multiple dose levels of DAN-222 as monotherapy and those also combined with niraparib. Results: Results were consistent in both the HRD+ and HRD- tumor models with profound dose-response of DAN-222 monotherapy inhibiting tumor growth. Additionally, synergy was demonstrated when DAN-222 was combined with niraparib, clearly evident with low doses of both products when used in combination. The table below highlights the synergy of the combination of DAN-222 at 0.3 mg/kg and niraparib at 25 mg/kg above each agent alone on the tumor growth inhibition in the MDA-MB-436 xenograft. Conclusions: Combining a PARP inhibitor with a topoisomerase I inhibitor delivered via this polymeric nanoparticle delivery system (DAN-222) has synergistic efficacy in both HRD+ and HRD- xenograft tumor models. These data support continued development of DAN-222 to treat solid tumors and its combination use with PARP inhibitors.[Table: see text]

scholarly journals The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis

Cell Cycle ◽  
2012 ◽  
Vol 11 (21) ◽  
pp. 3972-3982 ◽  
Author(s):  
Gloria Bonuccelli ◽  
Remedios Castello-Cros ◽  
Franco Capozza ◽  
Ubaldo E. Martinez-Outschoorn ◽  
Zhao Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Milk Protein ◽  
Cancer Tumor ◽  
Stat1 Signaling ◽  
Tumor Growth And Metastasis

Abstract 1410: PI3K inhibitors reduce breast cancer tumor growth and enhance anti-tumor leukocyte activity

2016 ◽  
Author(s):  
Nicole Lavender ◽  
Jinming Yang ◽  
Jiqing Sai ◽  
Sergey Novitskiy ◽  
Linda Horton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Pi3k Inhibitors ◽  
Leukocyte Activity ◽  
Cancer Tumor

scholarly journals Integrin α9 depletion promotes β‐catenin degradation to suppress triple‐negative breast cancer tumor growth and metastasis

2019 ◽  
Vol 145 (10) ◽  
pp. 2767-2780 ◽  
Author(s):  
Zhishan Wang ◽  
Yunfei Li ◽  
Yajuan Xiao ◽  
Hsuan‐Pei Lin ◽  
Ping Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Tumor ◽  
Tumor Growth And Metastasis

pcDNA3.1(−)-mediated ribozyme targeting of HER-2 suppresses breast cancer tumor growth

2009 ◽  
Vol 37 (3) ◽  
pp. 1597-1604 ◽  
Author(s):  
Pei He ◽  
Dan Zhu ◽  
Jun-Jian Hu ◽  
Ju Peng ◽  
Lian-Sheng Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Tumor ◽  
Her 2
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