Synergistic Effect of Alectinib and Everolimus on ALK-positive Anaplastic Large Cell Lymphoma Growth Inhibition

• Published in: Anticancer research 2020-03, Vol.40 (3), p.1395-1403
• Main Authors: Kim, Dongchan, Koh, Youngil, Yoon, Sung-Soo
• Format: Article
• Language: English
• Subjects: Anaplastic large-cell lymphoma; Anaplastic Lymphoma Kinase - antagonists & inhibitors; Anaplastic Lymphoma Kinase - biosynthesis; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Carbazoles - administration & dosage; Carbazoles - pharmacology; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell growth; Cell Growth Processes - drug effects; Cell Line, Tumor; Cell proliferation; Crizotinib - administration & dosage; Crizotinib - pharmacology; Drug Synergism; Everolimus - administration & dosage; Everolimus - pharmacology; G1 phase; Humans; Inhibitor drugs; Inhibitors; Jurkat Cells; Kinases; Lymphoma; Lymphoma, Large-Cell, Anaplastic - drug therapy; Lymphoma, Large-Cell, Anaplastic - enzymology; Lymphoma, Large-Cell, Anaplastic - pathology; Piperidines - administration & dosage; Piperidines - pharmacology; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - pharmacology; Protein-tyrosine kinase; Rapamycin; Synergistic effect; Targeted cancer therapy; TOR protein
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14081

The aim of the study was to examine the efficacy of the combination of anaplastic lymphoma kinase (ALK) inhibitors with other inhibitors for the treatment of ALK-positive lymphomas. This approach is predicted to be an alternative way for suppressing ALK-positive anaplastic large cell lymphoma (ALCL). We treated ALK-positive ALCL cell lines, KARPAS-299 and SU-DHL-1, with the ALK inhibitor alectinib and the mammalian target of rapamycin (mTOR) inhibitor everolimus. The ALK inhibitor alectinib had a selective ALK-dependent inhibitory effect on ALK-positive cancer cell proliferation. Treatment with alectinib or everolimus inhibited target molecules, and their combination augmented their inhibitory effect on the mTOR pathway. Furthermore, the combination treatment significantly inhibited cell proliferation and induced cell cycle arrest at the G /G phase in ALK-positive ALCL cells. The combination of both inhibitors synergistically inhibits ALK-positive ALCL cell growth via the ALK/mTOR pathway.