ILANIT 2023

Development Of new drug to treat chronic Lymphocytic Leukemia

Orly Aliza Spiegel 1,2 Eleonora Ela Hezkiy 1
1Department of Molecular Biology, Ariel University, Israel
2The University Unit for Children and Youth, Ariel University, Israel

Drug combinations are the present and the future of anticancer drug therapy. In this research we establish synergistic drug combinations with an FDA approved drug, ibrutinib, which is used to treat chronic lymphocytic leukemia (CLL) and other B cells malignancies. Ibrutinib is an oral drug, small molecule that inhibits Bruton tyrosine kinase (BTK) which is essential for B cells development. Despite ibrutinib’s promising activity, approximately 30% of patients have primary resistance to the drug while other patients develop secondary resistance. In order to raise the response of CLL patients to ibrutinib we suggest a combination of ibrutinib with mTORC1 inhibitor, Rapamycin. We examined this combination on CLL cells, MEC1 and A20. We showed that the rate of apoptosis in cell line MEC1 treated with combination ibrutinib and rapamycin was 88%, whereas ibrutinib and rapamycin alone were 61% and 65% respectively. Comparable results were also seen in A20 cell lines: 54%, 40.5% and 38%. These results show the effectiveness of ibrutinib and rapamycin combination and could be used together for treatment.