Response of a chemo-resistant triple-negative breast cancer patient to a combination of p62-encoding plasmid, Elenagen, and CMF chemotherapy
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Dmitry M. Ponomarenko1, Vladimir L. Gabai2,3,*, Albert A. Sufianov4,5, Sergey I. Kolesnikov6,7,8 and Alexander M. Shneider2,5,9,*
1 Irkutsk State Medical Academy of Postgraduate Education, Irkutsk Regional Cancer Dispensary, Irkutsk, Russian Federation
2 CureLab Oncology, Inc, Dedham, MA, USA
3 Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
4 Federal Center of Neurosurgery, Tyumen, Russian Federation
5 Sechenov First Moscow State Medical University, Moscow, Russian Federation
6 Russian Academy of Sciences, Moscow, Russian Federation
7 Lomonosov Moscow State University, Moscow, Russian Federation
8 Research Center of Family Health and Reproduct ion Problems, Irkutsk, Russian Federation
9 Department of Molecular Biology, Ariel University, Ariel, Israel
* These authors have contributed equally to this work
|Alexander M. shneider,||email:||[email protected]|
Keywords: cancer immunotherapy; cancer chemotherapy; p62 plasmid; cancer vaccine
Abbreviations: MSCT: multispiral computed tomography; TNBC: triple-negative breast cancer
Received: September 14, 2019 Accepted: October 19, 2019 Published: January 21, 2020
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.
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