Li, Y.; Sung, Y.; Choi, Y.E.; Choi, Y.; Goh, S.-H. Synergistic Enhancement of Antitumor Effects by Combining Abemaciclib with Desipramine. Int. J. Mol. Sci.2024, 25, 7407.
Li, Y.; Sung, Y.; Choi, Y.E.; Choi, Y.; Goh, S.-H. Synergistic Enhancement of Antitumor Effects by Combining Abemaciclib with Desipramine. Int. J. Mol. Sci. 2024, 25, 7407.
Li, Y.; Sung, Y.; Choi, Y.E.; Choi, Y.; Goh, S.-H. Synergistic Enhancement of Antitumor Effects by Combining Abemaciclib with Desipramine. Int. J. Mol. Sci.2024, 25, 7407.
Li, Y.; Sung, Y.; Choi, Y.E.; Choi, Y.; Goh, S.-H. Synergistic Enhancement of Antitumor Effects by Combining Abemaciclib with Desipramine. Int. J. Mol. Sci. 2024, 25, 7407.
Abstract
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, HER2-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have showed the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. The combination of abemaciclib and desipramine may be a promising therapeutic strategy as they could reduce side effects and enhance tumor suppression.
Keywords
abemaciclib; tricyclic antidepressant; combined therapy; in vivo
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
