Abstract
Triple-negative breast cancers are often characterized by aggressive behavior and short clinical course once they become chemotherapy-resistant. We describe below a patient who has shown a response to combination of chemotherapy with Elenagen, a plasmid encoding p62. Elenagen was tested in a previous phase I/II study in patients with refractory solid tumors and shown to be safe. Also, plasmid ability to halt tumor progression and restore sensitivity to chemotherapy was found. Preclinical data supports effects on tumor grade and change the tumor’s microenvironment in spontaneous canine breast cancers. We describe here a 48-year old female with triple-negative and BRCA1/2-negative breast cancer who had a primary resistance to chemotherapy and negative dynamics despite the use of multiple lines of treatments. Elenagen was applied intramuscularly at a dose of 1 mg weekly in combination with standard chemotherapy scheme CMF (cyclophosphamide, methotrexate, fluorouracil). In this patient we observed partial tumor regression (by 33%) and 19 weeks of progression-free survival. This first observed objective response to a combination of Elenagen with chemotherapy demonstrates that even in heavily pretreated chemo-resistant triple-negative tumor, the addition of Elenagen to a chemotherapy regimen can cause an objective response and increase in progression-free survival. Such a regimen is worthy of further study in a larger number of patients.
Highlights
Breast cancer is one of the most common tumors, and every year more than two million women in the world are diagnosed with it
We describe here a 48-year old female with triple-negative and BRCA1/2-negative breast cancer who had a primary resistance to chemotherapy and negative dynamics despite the use of multiple lines of treatments
For such receptor-negative cancers, chemotherapy is the method of choice, but there is no single standard approach [3]
Summary
Breast cancer is one of the most common tumors, and every year more than two million women in the world are diagnosed with it (https://www.wcrf.org/dietandcancer/ cancer-trends/breast-cancer-statistics). Among the subtypes of breast cancer, triple-negative breast cancers (TNBC) which does not express estrogen, progesterone and HER2 receptors account for 15% of cases and are characterized by low levels of differentiation of tumor cells and rapid aggressive growth [1, 2] For such receptor-negative cancers, chemotherapy is the method of choice, but there is no single standard approach [3]. The first is the creation of adaptive antitumor immunity against tumor-specific antigens, i.e. stimulating in patient's body more T-and B-lymphocytes against targets mainly represented in cancer cells, but not in other parts of the body This direction, in particular, includes DNA vaccines [8, 9]. Elenagen was started on Apr 2018 along with a standard CMF chemotherapy regimen: cyclophosphamide 600 mg/m2 i.v., methotrexate 40 mg/m2 i.v., fluorouracil 600 mg/m2 i.v., days 1st and 8th, 2-wk interval between www.oncotarget.com
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