Response of a chemo-resistant triple-negative breast cancer patient to a combination of p62-encoding plasmid, Elenagen, and CMF chemotherapy

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 chemoresistant 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.

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

“…Intriguingly, a p62 encoding plasmid named Elenagen was used in association with standard chemotherapy to treat a chemoresistant triple-negative breast cancer patient with significant improvement in the response and increase in progression-free survival [ 90 ].…”

“…In this regard, Liu et al showed that low nuclear level of p62 was associated with aggressive clinic pathologic features and unfavourable prognosis of oral squamous cell carcinoma [89]. Intriguingly, a p62 encoding plasmid named Elenagen was used in association with standard chemotherapy to treat a chemoresistant triple-negative breast cancer patient with significant improvement in the response and increase in progression-free survival [90].…”

Melatonin downregulates TRPC6, impairing store-operated calcium entry in triple-negative breast cancer cells

“…Among the breast cancer subtypes, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors and lack of excess of human epidermal growth factor receptor 2 (HER2) expression. TNBC accounts for about 15% of all breast cancer cases ( 2 ), and TNBC cells exhibit low levels of differentiation as well as rapid and aggressive proliferation ( 3 ). A number of cancer features in TNBC cells have been reported to depend on Ca 2+ influx across the plasma membrane.…”

Cancer Vaccines for Triple-Negative Breast Cancer: A Systematic Review

“…Accordingly, the same team reported the case of a heavily-pretreated, chemo-resistant TNBC patient treated with the combination of weekly Elenagen and cyclophosphamide/methotrexate/fluorouracil (CMF) chemotherapy. The patient experienced a 33% partial tumor regression and 19 weeks of PFS [ 65 ]. Considering these positive results, further studies of such combinations on larger TNBC patient populations are eagerly awaited.…”