Ponomarenko Dmitry M, Gabai Vladimir L, Sufianov Albert A, Kolesnikov Sergey I, Shneider Alexander M
Irkutsk State Medical Academy of Postgraduate Education, Irkutsk Regional Cancer Dispensary, Irkutsk, Russian Federation.
CureLab Oncology, Inc, Dedham, MA, USA.
Oncotarget. 2020 Jan 21;11(3):294-299. doi: 10.18632/oncotarget.27323.
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.
三阴性乳腺癌一旦对化疗产生耐药,通常具有侵袭性的行为和较短的临床病程。我们在下文描述了一名对化疗与Elenagen(一种编码p62的质粒)联合治疗有反应的患者。Elenagen在先前一项针对难治性实体瘤患者的I/II期研究中进行了测试,结果显示是安全的。此外,还发现了该质粒具有阻止肿瘤进展和恢复化疗敏感性的能力。临床前数据支持其对自发犬乳腺癌肿瘤分级的影响以及对肿瘤微环境的改变。我们在此描述一名48岁的女性,患有三阴性且BRCA1/2阴性乳腺癌,对化疗原发耐药,尽管接受了多线治疗但病情仍呈阴性进展。Elenagen以每周1毫克的剂量肌肉注射,与标准化疗方案CMF(环磷酰胺、甲氨蝶呤、氟尿嘧啶)联合使用。在该患者中,我们观察到肿瘤部分消退(33%)和19周的无进展生存期。首次观察到Elenagen与化疗联合治疗有客观反应,这表明即使在经过大量预处理的化疗耐药三阴性肿瘤中,在化疗方案中添加Elenagen也可引起客观反应并延长无进展生存期。这样的治疗方案值得在更多患者中进一步研究。