Targeting PLK1 as a Common Mechanism in Ph-like ALL

Background

As with many other cancers, acute lymphoblastic leukemia (ALL) cases are often driven by over-active proteins, called kinases. Although for some patients targeted therapy is available, many do not have appropriate agents available and many will not survive their disease. We are looking for common targetable pathways which are turned on by these kinases.

This proposal will show that Polo-like Kinase 1 (PLK1) is a new, targetable kinase, which may benefit a large subset (18-60%) of ALL patients, depending on age. PLK1 controls the growth of cells and it is over-expressed in multiple adult cancers. Our initial experiments reveal that blocking PLK1 stops the growth of human ALL cells and leads to their death. In addition, using this PLK1 inhibitor improves the efficacy of standard chemotherapy.

Project Goal

These studies provide support for clinical trials of PLK inhibitors in ALL, although which patients may benefit, how these PLK1 inhibitors work in ALL, and the best way to use them with other ALL treatments is still unknown. The ultimate goal of this proposal is to provide comprehensive evidence that PLK1 inhibitors should be used to treat children, adolescents and young adults with these kinase-driven ALLs.

Project Update 2020

Our work has focused on Polo-like Kinase 1 (PLK1), which is a new, targetable kinase and is active in a large subset (18-60%) of ALL patients. We have shown that blocking PLK1 stops the growth of human ALL cells and leads to their death. In addition, using a PLK1 inhibitor improves the efficacy of standard chemotherapy. By examining proteins changed by PLK1 inhibition, we are learning what subsets of ALL might benefit most from PLK1 inhibitors, and we are also anticipating how to over drug resistance to PLK1 directed therapies. These studies provide support for clinical trials of PLK inhibitors in ALL by determining which patients may benefit, how these PLK1 inhibitors work in ALL, and the best way to use them with other ALL treatments.