**5. Conclusions**

Collectively, our data illustrates that inhibition of AKT-signaling pathway STS and GIST might be considered as a potent tool to enhance their sensitivity to doxorubicin, a topoisomerase II inhibitor. This might be due to the attenuation of homology-mediated DNA repair in AKT-inhibited tumor cells. In particular, we observed the decrease of Rad51 on the protein level in AKT-inhibited cells and attenuated recruitment of Rad51 recombinase to the chromatin and the sites of DSBs after Dox treatment. As a consequence of attenuation of homology-mediated repair of DNA DSBs, AKT-inhibited tumor cells underwent the apoptotic cell death after Dox treatment, which was evidenced by increases expression of well-known apoptotic markers—cleaved forms of caspase-3 and PARP.

**Supplementary Materials:** Supplementary materials can be found at http://www.mdpi.com/1422-0067/21/22/8842/s1.

**Author Contributions:** Conception and design: S.B.; Development of methodology: S.B., A.G., F.B., A.A., P.D., E.V., I.N., A.S.; Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): S.B., A.G., F.B., A.A., P.D., E.V., I.N., A.S.; Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): S.B., A.G., F.B., A.A., P.D., I.N.; Writing, review and/or revision of the manuscript: S.B.; Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): S.B.; Study supervision: S.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** This study was supported by grant from Russian Science Foundation (RSF) (grant No. 20-15-00001).

**Acknowledgments:** We thank Kirill Syuzov for assistance in the statistical analysis.

**Conflicts of Interest:** The authors declare no conflict of interest.
