ПРОТИВООПУХОЛЕВОЕ ДЕЙСТВИЕ ИНДУКТОРОВ ФЕРРОПТОЗА НА ОРГАНОИДЫ МЕТАСТАТИЧЕСКОГО КОЛОРЕКТАЛЬНОГО РАКА

Биотехнология. 2023. Т. 39. № 6. С. 73–83.

Razumovskaya A., Silkina M., Кулагин Т. А., Nikulin S., Slobodov S., Stepanova E., Алексеев Б. Я.

To date, colorectal cancer (CRC) remains one of the most common malignant neoplasms worldwide with a high mortality rates. In recent decades, progress in the study of the mechanisms underlying drug resistance in CRC confirmed the need to search for new therapeutic approaches. In particular, tumor cells that are resistant to standard therapy and to classical mechanisms of programmed cell death, such as apoptosis, are known to be sensitive to ferroptosis. Therefore, induction of ferroptosis is considered as a promising alternative means of controlling cancer cells. In this work, the effects of the known ferroptosis inducers erastin and sorafenib, both as monotherapy and in combination with standard chemotherapeutic drugs used for treatment of CRC, were studied on cultures of tumor organoids of metastatic CRC obtained previously from three patients. The results indicate that the ferroptosis inducers, erastin and sorafenib, display antitumor activity. Moreover, they can enhance the effects of standard chemotherapeutic drugs on organoid cultures of metastatic CRC. Thus, induction of ferroptosis in CRC tumor tissue in additional to standard therapy may be a promising therapeutic option and deserves further investigation in preclinical and clinical settings.

Keywords: колоректальный рак, Colorectal cancer, опухолевые органоиды, Patient-derived organoids, ferroptosis, ферроптоз, erastin, sorafenib, эрастин, сорафениб