STUDY OF THE EFFECT OF LOMUSTIN ON HER2-POSITIVE BREAST CANCER IN FVB/N HER-2 TRANSGENIC MICE
https://doi.org/10.21294/1814-4861-2019-18-5-54-60
Abstract
Because of the high risk of brain metastases from HER2-positive breast cancer, the study of the anticancer activity of drugs used to treat brain tumors, in particular lomustine, is of great importance. In the FVB/N Her-2 transgenic mice bearing HER2-positive breast cancer (BC HER2+), a single oral administration of lomustine at a dose of 50 mg/kg resulted in a significant tumor growth inhibition (up to 96 %, p<0.0001). The tumor growth index (TGI) expressed as a ratio between the areas under the kinetic curves of tumor growth in the study and control groups and amounted to 33 % (p<0.001) indicated the high activity of lomustine. However, the effect of lomustine on intramuscularly transplanted Ehrlich tumor was insignificant (tumor growth inhibition and tumor growth index were <39 % and 68 %, respectively). Lomustine administered orally at a single dose of 50 mg/kg 24 hours after intracranial transplantation of BC HER2+ increased the median survival time up to 30 days in FVB/N mice compared to 21 days in the control group mice (p<0.001). The high therapeutic effect of lomustine in HER2-positive breast cancer mice is likely can be explained by the biological characteristics of this tumor; therefore clinical trials of lomustine for HER2-positive tumors are needed.
Keywords
About the Authors
A. N. StukovRussian Federation
Alexander N. Stukov, MD, DSc, Senior Researcher, Department of Innovative Methods of Therapeutic Oncology and Rehabilitation
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 7004016508
S. F. Vershinina
Russian Federation
Sofia F. Vershinina, DSc, Leading Researcher
70, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 7004111804
N. A. Koziavin
Russian Federation
Nikita A. Koziavin, MD, Physician
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
T. Yu. Semiglazova
Russian Federation
Tatiana Yu. Semiglazova, MD, DSc, Head of Department of Innovative Methods of Therapeutic Oncology and Rehabilitation
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 8562948700
L. V. Filatova
Russian Federation
Larisa V. Filatova, MD, DSc, Leading Researcher, Department of Innovative Methods of Therapeutic Oncology and Rehabilitation
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 18334377100
D. Kh. Latipova
Russian Federation
Dilorom Kh. Latipova, MD, PhD
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 50961448800
A. O. Ivantsov
Russian Federation
Alexander O. Ivantsov, MD, PhD, Leading Researcher
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 26025936100
V. G. Bespalov
Russian Federation
Vladimir G. Bespalov, MD, DSc, Head of Laboratory for Cancer Chemoprevention and Oncopharmacology
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 56921601600
A. L. Semenov
Russian Federation
Alexander L. Semenov, Researcher, Laboratory for Cancer Chemoprevention and Oncopharmacology
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 16307589600
O. A. Belyaeva
Russian Federation
Olesya A. Belyaeva, PhD
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 54993582100
G. S. Kireeva
Russian Federation
Galina S. Kireeva, PhD, Senior Researcher, Laboratory for Carcinogenesis and Aging
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
SPIN-код: 5643-6973
Author ID (Scopus): 56184283000
V. A. Alexandrov
Russian Federation
Valery A. Alexandrov, MD, DSc, Leading Researcher, Laboratory for Cancer Chemoprevention and Oncopharmacology
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 7006723656
G. V. Tochilnikov
Russian Federation
Grigoriy V. Tochilnikov, MD, PhD, Senior Researcher, Laboratory for Cancer Chemoprevention and Oncopharmacology
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 57194493773
I. N. Vasilyeva
Russian Federation
Irina N. Vasilyeva, PhD, Senior Researcher, Laboratory for Cancer Chemoprevention and Oncopharmacology
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 7003273722
M. A. Maydin
Russian Federation
Mikhail A. Maydin, Researcher, Laboratory for Carcinogenesis and Aging
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 56184141100
M. L. Tyndyk
Russian Federation
Margarita L. Tyndyk, PhD, Senior Researcher, Laboratory for Carcinogenesis and Aging
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 6602634277
S. S. Kruglov
Russian Federation
Stepan S. Kruglov, Researcher, Laboratory for Carcinogenesis and Aging
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
G. A. Yanus
Russian Federation
Grigory A. Yanus, MD, PhD, Senior Researcher, Laboratory of Molecular Oncology, N.N. Petrov National Medical Research Center of Oncology
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg,
2, Litovskaya Street, 194100, St. Petersburg
Author ID (Scopus): 36011349100
V. N. Yurova
Russian Federation
Maria N. Yurova, PhD, Senior Researcher, Laboratory for Carcinogenesis and Aging
68, Leningradskaya Street, Pos. Pesochny, 197758, St. Petersburg
Author ID (Scopus): 6602814066
References
1. Tan M., Yu D. Molecular mechanisms of erbB2-mediated breast cancer chemoresistance. Adv Exp Med Biol. 2007; 608: 119–129. doi: 10.1007/978-0-387-74039-3_9.
2. Tryakin A.A. Target therapy of colorectal cancer, gastric cancer and pancreas. Practical Oncology. 2010; 11(3): 143–150. (in Russian).
3. Santin A.D., Bellone S., Roman J.J., McKenney J.K., Pecorelli S. Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu. Int J Gynaecol Obstet. 2008 Aug; 102(2): 128–31. doi: 10.1016/j.ijgo.2008.04.008.
4. Pestalozzi B.C., Holmes E., de Azambuja E., Metzger-Filho O., Hogge L., Scullion M., Láng I., Wardley A., Lichinitser M., Sanchez R.I., Müller V., Dodwell D., Gelber R.D., Piccart-Gebhart M.J., Cameron D. CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol. 2013 Mar; 14(3): 244–8. doi: 10.1016/S1470-2045(13)70017-2.
5. Barnholtz-Sloan J.S., Sloan A.E., Davis F.G., Vigneau F.D., Lai P., Sawaya R.E. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004; 22(14): 2865–2872. doi: 10.1200/JCO.2004.12.149.
6. Krop I.E., Lin N.U., Blackwell K., Guardino E., Huober J., Lu M., Miles D., Samant M., Welslau M., Diéras V. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol. 2015 Jan; 26(1): 113–9. doi: 10.1093/annonc/mdu486.
7. Tyndyk M.L., Popovich I.G., Anikin I.V., Egormin P.A., Yurova M.N., Zabezhinsky M.A., Anisimov V.N. SSH&H influence on the lifespan and spontaneous cancer development in transgenic mice with HER-2/neu mutation. Problems in Oncology. 2012; 58 (2): 243–247. (in Russian).
8. Panchenko A.V., Popovich I.G., Trashkov A.P., Egormin P.A., Yurova M.N., Tyndyk M.L., Gubareva E.A., Artyukin I.N., Vasiliev A.G., Khaitsev N.V., Zabezhinski M.A., Anisimov V.N. Biomarkers of aging, life span and spontaneous carcinogenesis in the wild type and HER-2 transgenic FVB/N female mice. Biogerontology. 2016 Apr; 17(2): 317–24. doi: 10.1007/s10522-015-9611-y.
9. Stukov A.N., Filatova L.V., Latipova D.Kh., Bespalov V.G., Belyaeva O.A., Kireeva G.S., Vasilieva I.N., Alexandrov V.A., Maidin M.A., Semenov A.L., Vershinina S.F., Markochev A.B., Abduloeva N.Kh., Chubenko V.A., Semiglazova T.Yu. Therapeutic activity of gemcitabine in intracranial tumors. Problems in Oncology. 2015; 61(2): 274–279. (in Russian).
10. Stukov A.N., Ivanova M.A., Nikitin A.K., Sorokin G.M., Kon’kov S.A. Tumor growth index as an integral criterion for the effectiveness of antitumor therapy in an experiment. Problems in Oncology. 2001; 47(5): 616–618. (in Russian).
Review
For citations:
Stukov A.N., Vershinina S.F., Koziavin N.A., Semiglazova T.Yu., Filatova L.V., Latipova D.Kh., Ivantsov A.O., Bespalov V.G., Semenov A.L., Belyaeva O.A., Kireeva G.S., Alexandrov V.A., Tochilnikov G.V., Vasilyeva I.N., Maydin M.A., Tyndyk M.L., Kruglov S.S., Yanus G.A., Yurova V.N. STUDY OF THE EFFECT OF LOMUSTIN ON HER2-POSITIVE BREAST CANCER IN FVB/N HER-2 TRANSGENIC MICE. Siberian journal of oncology. 2019;18(5):54-60. https://doi.org/10.21294/1814-4861-2019-18-5-54-60