PROSPECTS FOR THE USE OF PARP-INHIBITORS IN ADVANCED GASTRIC CANCER

K.V. Menshikov1,2, A.V. Sultanbaev1, R.R. Rakhimov1, A.A. Izmaylov1,2, Sh.I. Musin1, I.A. Menshikova2, R.R. Urazin1, N.I. Sultanbaeva1, A.F. Nasretdinov1, D.O. Lipatov2

1Republican Clinical Oncology Dispensary, Ufa

2Bashkir State Medical University, Ufa

Sultanbaev Aleksandr V. ― Cand. of Sci. (Med.), oncologist, Head of the Department of Anticancer Drug Therapy of Republican Clinical Oncology Dispensary

73/1 Oktyabrya Ave., Ufa, 450054, Russian Federation, e-mail: rkodrb@yandex.ru, ORCID ID: 0000-0003-0996-5995

Abstract. Gastric cancer is one of the most common types of malignant neoplasms, it also remains one of the leading causes of death from malignant neoplasms worldwide. High incidence is observed in regions such as Asia, Central and Eastern Europe, South America. In the Russian Federation, malignant neoplasms of the stomach occupy the fourth place. In the Republic of Bashkortostan, 695 patients with malignant neoplasms of the stomach were registered in 2020. Of the identified patients, 41.2% had stage IV disease and were not candidates for radical surgical treatment. Mortality in the first year of life from the moment of diagnosis was 49.8%. The only possible treatment option in such cases is systemic anticancer therapy, which can increase survival and reduce one-year mortality. An important link here is the use of innovative drugs, which include PARP-inhibitors. Positive results of the use of PARP-inhibitors in patients with mutations in DNA repair genes in the treatment of breast cancer, ovarian cancer and prostate cancer have been noted. The place of PARP-inhibitors in the treatment of advanced gastric cancer has not yet been fully elucidated, but recent data indicate new possibilities of using PARP-inhibitors in the treatment of refractory gastric cancer. In a tumor with deficiency in DNA repair due to loss of ATM protein expression, patients may benefit from treatment with PARP inhibitors. The mechanism of action of PARP-inhibitors in gastric cancer is currently not fully understood. They remain a topic for discussion and scientific research and predictors of the effectiveness of this therapy.

Key words: PARP-inhibitors, olaparib, gastric cancer, germline mutations, somatic mutations.