ONC201, an anti-cancer drug that triggers cell death in various tumor types, may be effective in treating some blood cancers, including mantle cell lymphoma (MCL) and acute myeloid leukemia (AML), according to a recent clinical study.
A research team led by Michael Andreeff, M.D., Ph.D., professor of Leukemia at MD Anderson Cancer Center, found that ONC201, which is in early clinical trials, caused cell death even when a crucial protein known as p53 is mutated or deleted entirely. This dysfunction occurs in more than half of malignancies and can promote malignant characteristics of cancers as well as resistance to standard chemotherapy, raising an urgent need for novel therapeutic solutions.
The study results were published online issue in Science Signaling.
ONC201 is a first-in-class drug being clinically developed by Oncoceutics Inc. and MD Anderson. The drug is of interest because of its ability to kill cancer cells without harming healthy cells. Previously, Andreeff and others conducted extensive pre-clinical studies of ONC201.
“The clinical challenge posed by p53 abnormalities in blood malignancies is that therapeutic strategies other than standard chemotherapies are required,” said Andreeff. “We found that ONC201 caused p53-independent cell death and cell cycle arrest in cell lines and in lymphoma and acute leukemia patient samples.”
The patient samples included those that demonstrated genetic abnormalities linked to a poor prognosis or cells that developed resistance to the drugs ibrutinib and bortezomib, which are commonly used for lymphoma and multiple myeloma patients. Additionally, mice studies revealed that ONC201 caused cell death in AML and leukemia stem cells, but appeared to spare normal bone marrow cells.
Read more about Dr. Andreeff's study involving ONC201 on MD Anderson's website.