Abstract IA13: Combination of DNA methyltransferase and PARP inhibitors as a novel therapy strategy for multiple cancers: Key data in AML and triple negative breast cancer

Author(s):  
Nidal Muvarak ◽  
Khadiza Chowdhury ◽  
Carine Robert ◽  
Xia Limin ◽  
Eun Yong Choi ◽  
...  
2020 ◽  
Vol 7 (1) ◽  
pp. 55-65
Author(s):  
A. A. Kharitonova ◽  
I. A. Smirnova ◽  
M. V. Kiseleva

By far the most aggressive subtype of breast cancer is triple negative cancer. The purpose of this review is to analyze current ideas about the pathogenesis, clinical characteristics of different subtypes of triple negative breast cancer, the nature of its metastasis, mechanisms of chemoresistance. The review presents the results of modern regimens of drug therapy of triple negative breast cancer according to the publications of domestic and foreign oncologists. On the basis of various clinical studies, the effectiveness of the use of anthracyclines, taxanes in the dose-dense regime, platinum preparations and other chemotherapy drugs for the treatment of triple-negative cancer has been shown. The presented treatment regimens allow to achieve a complete morphological response in 85% of patients, to increase the rates of relapse-free and overall survival, comparable with other subtypes of breast cancer. The review highlights the possibilities of modern targeted drugs-PARP inhibitors, chk1 inhibitors UCN‑01, immunotherapy possibilities for the treatment of this aggressive subtype of breast cancer.


2021 ◽  
Vol 23 (1) ◽  
pp. 78-81
Author(s):  
Inna P. Ganshina ◽  
Olga O. Gordeeva ◽  
Mariam S. Manukyan

Metastatic triple negative breast cancer (mTNBC) is a difficult task for the chemotherapist in view of the disease aggressiveness, biological heterogeneity of the tumor, as well as the limit of therapy options. The approved modern drugs, such as immunotherapy and PARP inhibitors, have improved the treatment results in women with mTNBC. However, not all women are the candidates for this kind of therapy due to the lack of suitable points of application. In this context, high hopes are placed on the new treatment options currently being studied in clinical trials. The review summarizes data on advanced drugs that have demonstrated their efficacy in this multiplex group of women, but not yet registered at the territory of the Russian Federation Russian Federation, and will allow us to form an idea of the future algorithm of treatment of women with mTNBC.


Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1864 ◽  
Author(s):  
Holly Tovey ◽  
Maggie Chon U. Cheang

The concept of precision medicine has been around for many years and recent advances in high-throughput sequencing techniques are enabling this to become reality. Within the field of breast cancer, a number of signatures have been developed to molecularly sub-classify tumours. Notable examples recently approved by National Institute for Health and Care Excellence in the UK to guide treatment decisions for oestrogen receptors (ER)+ human epidermal growth factor receptor 2 (HER2)- patients include Prosigna® test, EndoPredict®, and Oncotype DX®. However, a population of still unmet need are those with triple negative breast cancer (TNBC). Accounting for 15–20% of patients, this population has comparatively poor prognosis and as yet no targeted treatment options. Studies have shown that some patients with TNBC respond favourably to DNA damaging drugs (carboplatin) or agents which inhibit DNA damage response (poly ADP ribose polymerase (PARP) inhibitors). Known to be a heterogeneous population, there is a need to identify further TNBC patients who may benefit from these treatments. A number of signatures have been identified based on association with treatment response or specific genetic features/pathways however many of these were not restricted to TNBC patients and as of yet are not common practice in the clinic.


2019 ◽  
Vol 20 (16) ◽  
pp. 1151-1157 ◽  
Author(s):  
Jia Yu ◽  
Jacqueline Zayas ◽  
Bo Qin ◽  
Liewei Wang

Triple-negative breast cancer (TNBC) accounts for 15–20% of all invasive breast cancers and tends to have aggressive histological features and poor clinical outcomes. Unlike, estrogen receptor- or HER2-positive diseases, TNBC patients currently lack the US FDA-approved targeted therapies. DNA methylation is a critical mechanism of epigenetic modification. It is well known that aberrant DNA methylation contributes to the malignant transformation of cells by silencing critical tumor suppressor genes. DNA methyltransferase inhibitors reactivate silenced tumor suppressor genes and result in tumor growth arrest, with therapeutic effects observed in patients with hematologic malignancies. The antitumor effect of these DNA methyltransferase inhibitors has also been explored in solid tumors, especially in TNBC that currently lacks targeted therapies.


Oncoscience ◽  
2019 ◽  
Vol 6 (1-2) ◽  
pp. 287-288 ◽  
Author(s):  
Michèle Beniey ◽  
Takrima Haque ◽  
Saima Hassan

2019 ◽  
Vol 7 ◽  
pp. 232470961986498 ◽  
Author(s):  
Trevanne Matthews Hew ◽  
Lara Zuberi

Triple-negative breast cancer (TNBC) accounts for 20% of breast cancers diagnosed worldwide. This subtype of breast cancer tends to behave more aggressively, and unlike other breast cancer subtypes, there are no standard targeted treatments for most patients. However, up to 20% of patients with TNBC harbor a breast cancer gene (BRCA) mutation, particularly in BRCA1. For patients who carry this gene mutation, this opens the door for new management options by the use of newer agents such as polyadenosine diphosphate-ribose polymerase (PARP) inhibitors in the metastatic setting. Given that this is uncommon and that PARP inhibitors have only recently received Federal Drug Administration approval, the experience with these drugs is relatively new. In this article, we present a case of a patient treated in this setting with olaparib who developed an unanticipated side effect as a result of the high efficacy of the drug.


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