ACHE TEST-SYSTEM FOR INDIVIDUALIZATION OF NEOADJUVANT POLYCHEMOTHERAPY

A comparative analysis of the chemotherapy drug effects on the enzymatic activity of breast cancer (BC) cells in a tumor primary culture of BC patients and a clinical response of a cancer tumor to neoadjuvant polychemotherapy (NPHT) with the use of the same drugs were performed. We used our developed test to assess the sensitivity of BC cells to chemotherapy drugs by determining the cell activity of acetylcholinesterase (AChE). The effect of chemotherapeutic drugs in culture and the clinical examination of BC patients of various molecular-genetic subtypes (Luminal A, Luminal B, Her2-positiv and Tripl-negativ or Basal-like) were compared. It is found that the coincidence of the results on the sensitivity of tumor cells in vitro and the degree of the patient’s tumor regression after NPHT averaged for X-ray examination is 69 %, manual – 77 % and US – 62 %. The biggest coincidence of the studied parameters was obtained for the most aggressive molecular-genetic subtypes of BC. Our developed test of assessment of the molecular chemotherapy effect on cells in vitro is the prognostic factor inexpensive and affordable for use in clinical laboratories when optimizing the patient treatment strategy.

breast cancer, acetylcholinesterase activity, breast cancer primary culture, tumor response to neoadjuvant polychemotherapy

1. Stenina M. B., Frolova M. A. Breast cancer: the most important scientific events and conclusion of recent years. Prakticheskaia onkologiia [Practical Oncology], 2011, vol. 12, no. 1, pp. 6-11. (in Russian).

2. Perou C. M. Molecular stratification of triple-negative breast cancers. Oncologist, 2010, vol. 15, suppl. 5, pp. 39-48.

3. Enzyme Nomenclature. Recommendations (1972) of the commission on biochemical nomenclature of the nomenclature and classification of enzymes, Amsterdam, Elsevier Publishing Company, 1973.

4. Bartolini M., Bertucci C., Cavrini V., Andrisano V. Beta-amyloid aggregation induced by human acetylcholiesterase: inhibition studies. Biochemical Pharmacology, 2003, vol. 65, no. 3, pp. 407-416.

5. Silman I., Sussman J. L. Acetylcholinesterase: «classical» and «non-classical» functions and pharmacology. Current Opinion in Pharmacology, 2005, vol. 5, pp. 293-302.

6. Barbosa M., Rios O., Velasques M., Villalobos J., Ehrmanns J. Acetylcholinesterase and butyrylcholinesterase histochemical activities and tumor cell growth in several brain tumors. Surgical Neurology, 2001, vol. 55, no. 2, pp. 106-112.

7. Musoz-Delgado E., Montenegro M. F., Campoy F. J., Moral-Naranjo M. T., Cabezas-Herrera J., Kovacs G., Vidal C. J. Expression of cholinesterases in human kidney and its variation in renal cell carcinoma types. FEBS Journal, 2010, vol. 277, no. 21, pp. 4519-4529.

8. Martinez-Moreno P., Nieto-Ceron S., Torres-Lanzas J., Ruiz-Espejo F., Tovar-Zapato I., Martinez-Hernandez P., Rodriguez-Lopez J. N., Vidal C. J., Cabezas-Herrera J. Cholinesterase activity of human lung tumours varies according to their histological classification. Carcinogenesis, 2006, vol. 27, no. 3, pp. 429-436.

9. Ruiz-Espejo F., Cabezas-Herrera J., Illana J., Campoy F. J., Vidal C. J. Cholinesterase activity and acetylcholinesterase glycosylation are altered in human breast cancer. Breast Cancer Research Treatment, 2002, vol. 72, no. 1, pp. 11-22.

10. Shukanova N. A., Martynova M. A., Putyrsky L. A., Putyrsky Iu. L., Kazlouskaia N. A., Bushmakina I. M., Molchan M. M. Comparative analysis of the reaction of malignantly transformed cells to chemotherapy in primary culture and post-therapeutic changes in the tumor of patients diagnosed with breast cancer. Molekuliarnye, membrannye i kletochnye osnovy funktsionirovaniia biosistem: Mezhdunarodnaia nauchnaia konferentsiia; Desiatyi s’ezd Belorusskogo obshchestvennogo ob’edineniia fotobiologov [Molecular, membrane and cellular bases of biosystem functioning: International scientific conference; The Tenth congress of the Belarusian public association of photobiologists and biophysicists]. Minsk, 2012, part 1, pp. 405-408. (in Russian).

11. Furukawa N., Kubota T., Hoffman R. M. Clinical application of the histoculture drug response assay. Clinical Cancer Research, 1995, vol. 1, pp. 305-311.

12. Ischenko R. V. Technique of drop/plasma culturation of tumor tissues for snap analysis of individual susceptibility to chemodrugs. Onkologiia [Oncology], 2002, vol. 4, no. 1, pp. 15-17. (in Russian).

13. Ellman G. L., Courtneuy K., Andres V. A new and rapid calorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 1961, vol. 7, no. 2, pp. 88-93.

14. Lowry O. H., Rosebrough H. L., Farr A. L., Randall P. J. Protein measurement with the Folin phenol reagent. Journal Biological Chemistry, 1951, vol. 193, no. 1, pp. 265-275.

15. Le Du F., Eckhardt B. L., Lim B., Litton J. K., Moulder S., Meric-Bernstam F., Gonzalez-Angulo A. M., Ueno N. T. Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype? Oncotarget, 2015, vol. 6, no. 15, pp. 12890-12908.

16. Bertheau P., Lerebours F., Nicolas Mounier N., de Roquancourt A., Espii M., Clot P., Servant J.-M., Misset J.-L., Marty M., Janin F. Prognostic significance of a combined clinicopathologic score for response to primary systemic therapy in locally advanced breast cancer. Oncology Report, 2005, vol. 14, no. 2, pp. 513-520.

17. Schott A. F., Roubidoux M. A., Helvie M. A., Hayes D. F., Kleer C. G., Newman L. A., Pierce L. J., Griffith K. A., Murray S., Hunt K., Paramagul C., Baker L. H. Clinical and radiologic assessments to predict breast cancer pathologic complete response to neoadjuvant chemotherapy. Breast Cancer Research Treatment, 2005, vol. 92, no. 3, pp. 231-231. https://doi.org/10.1007/s10549-005-2510-1.