A leukemia organoid platform for dissection and targeting of tumor-niche interactions
Progress in the treatment of childhood leukemia has been curtailed by the limited success of drugs tested in immortal leukemia cells, which after years of culture in the laboratory have lost much of the properties characteristic of the original tumor that they were derived from. The expansion of patient leukemia cells in specialized mice offers an improved alternative for identification of new effective drugs, but this approach is cumbersome and slow limiting its broad applicability. In recent years, a new system for cancer cell culture in the lab known as “tumor organoids” has accelerated the pace of drug discovery in solid tumors by enabling researchers to test the effects of new therapies in cancer cells grown in conditions that largely recapitulate those present the original tumor in body. We propose to develop an organoid system capable of supporting the growth of leukemia cells in the lab to accelerate the pace of drug discovery in this disease.
This project seeks to overcome current barriers in leukemia research by developing specialized platform capable of growing patient-derived leukemia cells in the lab. Towards this goal we will grow leukemia cells together with the bone and blood vessel cells that support their growth and proliferation in the body. Using this advanced approach that optimizes leukemia growth conditions in an environment that closely recapitulates the situation in the clinic, we will test the therapeutic effects of new drugs and genetic manipulations directed against central mechanisms of leukemia growth and survival. Ultimately, these studies will be instrumental for the development of novel therapies for the treatment of this high-risk leukemia patients.