The field of epigenetics focuses on changes in gene expression that do not come from alterations in the gene sequence. Instead, epigenetic modifications result from alterations in how DNA is regulated or transcribed. These modifications often play an important role in the formation and growth of tumors, and, as such, drugs that block tumor growth through the inhibition of epigenetic functions increasingly are becoming an effective approach in targeted therapies. Several of these epigenetic drugs have already received approval, especially for blood cancers. In this project, a team led by Philip Jones at the Institute for Applied Cancer Science at MD Anderson Cancer Center is focused on developing a clinical candidate targeting the epigenetic regulator CBP/p300 in subtypes of two blood cancers: acute myeloid leukemia (AML) and diffuse large B cell lymphoma (DLBCL).
There is currently only one CBP/p300 inhibitor in clinical trials, which is being evaluated for treating castration-resistant prostate cancer. The clinical candidate developed during this Drug Discovery Partnership could be the first CBP/p300 inhibitor to be tested clinically in genetically defined leukemias, which the investigators have identified as an important area of unmet need. Medicinal chemistry research and preclinical testing in cell cultures and mouse models have already suggested several potential candidates, but additional in vivo data, including data from patient-derived xenograft models, are needed to identify the best compound and to prepare an Investigational New Drug application. The initial clinical trials for this drug will focus on treating people with relapsed and/or refractory fusion-driven AML and people with relapsed and/or refractory DLBCL.