scholarly journals Biological Modulation of Parp Inhibition in Triple Negative Breast Cancer, a Combinational Approach Implementing Multitargeted Epigenetic Therapy (Mtet) with Parp Inhibition, in Advanced Breast Cancer: A Case Study

2018 ◽  
Vol 09 (09) ◽  
pp. 729-739
Author(s):  
M. Nezami ◽  
Steve Hager ◽  
Julie Taguchi
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Advanced Breast ◽  
Parp Inhibition ◽  
Epigenetic Therapy

scholarly journals Effect of Oxaliplatin, Olaparib and LY294002 in Combination on Triple-Negative Breast Cancer Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 2056
Author(s):  
Kitti Andreidesz ◽  
Balazs Koszegi ◽  
Dominika Kovacs ◽  
Viola Bagone Vantus ◽  
Ferenc Gallyas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Combined Treatment ◽  
Parp Inhibition ◽  
Akt Pathway ◽  
Platinum Compound ◽  
Mcf7 Cells ◽  
Cancer Line

Triple-negative breast cancer (TNBC) has a poor prognosis as the therapy has several limitations, most importantly, treatment resistance. In this study we examined the different responses of triple-negative breast cancer line MDA-MB-231 and hormone receptor-positive breast cancer line MCF7 to a combined treatment including olaparib, a poly-(ADP ribose) polymerase (PARP) inhibitor, oxaliplatin, a third-generation platinum compound and LY294002, an Akt pathway inhibitor. We applied the drugs in a single, therapeutically relevant concentration individually and in all possible combinations, and we assessed the viability, type of cell death, reactive oxygen species production, cell-cycle phases, colony formation and invasive growth. In agreement with the literature, the MDA-MB-231 cells were more treatment resistant than the MCF7 cells. However, and in contrast with the findings of others, we detected no synergistic effect between olaparib and oxaliplatin, and we found that the Akt pathway inhibitor augmented the cytostatic properties of the platinum compound and/or prevented the cytoprotective effects of PARP inhibition. Our results suggest that, at therapeutically relevant concentrations, the cytotoxicity of the platinum compound dominated over that of the PARP inhibitor and the PI3K inhibitor, even though a regression-based model could have indicated an overall synergy at lower and/or higher concentrations.

scholarly journals Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5432
Author(s):  
Luis de la Cruz-Merino ◽  
María Gion ◽  
Josefina Cruz-Jurado ◽  
Vanesa Quiroga ◽  
Raquel Andrés ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Treatment Efficacy ◽  
Triple Negative ◽  
Objective Response ◽  
Suppressor Cells ◽  
Primary Objective ◽  
Advanced Breast ◽  
Breast Cancer Patients

The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.

scholarly journals 4th International Consensus Conference on Advanced Breast Cancer (ABC4), Lisbon, November 4, 2017

2018 ◽  
Vol 78 (05) ◽  
pp. 469-480
Author(s):  
Michael Untch ◽  
Rachel Würstlein ◽  
Norbert Marschner ◽  
Diana Lüftner ◽  
Doris Augustin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Consensus Conference ◽  
Advanced Breast ◽  
Diagnosis And Treatment ◽  
Parp Inhibition ◽  
Molecular Testing ◽  
The World

AbstractThe fourth international advanced breast cancer consensus conference (ABC4) on the diagnosis and treatment of advanced breast cancer (ABC) headed by Professor Fatima Cardoso was once again held in Lisbon on November 2 – 4, 2017. To simplify matters, the abbreviation ABC will be used hereinafter in the text. In clinical practice, the abbreviation corresponds to metastatic breast cancer or locally far-advanced disease. This year the focus was on new developments in the treatment of ABC. Topics discussed included the importance of CDK4/6 inhibition in hormone receptor (HR)-positive ABC, the use of dual antibody blockade to treat HER2-positive ABC, PARP inhibition in triple-negative ABC and the potential therapeutic outcomes. Another major area discussed at the conference was BRCA-associated breast cancer, the treatment of cerebral metastasis, and individualized treatment decisions based on molecular testing (so-called precision medicine). As in previous years, close cooperation with representatives from patient organizations from around the world is an important aspect of the ABC conference. This cooperation was reinforced and expanded at the ABC4 conference. A global alliance was founded at the conclusion of the consensus conference, which aims to promote and coordinate the measures considered necessary by patient advocates worldwide. Because the panel of experts was composed of specialists from all over the world, it was inevitable that the ABC consensus also reflected country-specific features. As in previous years, a team of German breast cancer specialists who closely followed the consensus voting of the ABC panelists in Lisbon and intensively discussed the votes has therefore commented on the consensus in the context of the current German guidelines on the diagnosis and treatment of breast cancer 1, 2 used in clinical practice in Germany. The ABC consensus is based on the votes of the ABC panelists in Lisbon.

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