Researchers from The University of Texas MD Anderson Cancer Center (MD Anderson) have recently released study findings suggesting that the DAPK1 (death-associated protein kinase 1) protein is crucial for tumor growth in breast and other cancers with mutations in the TP53 gene and that it may be an efficacious therapeutic target for many of the most aggressive cancers. The study, entitled, “Death-associated protein kinase 1 promotes growth of p53-mutant cancers,” was published in the latest edition of the Journal of Clinical Investigation.
The current prognosis for Estrogen receptor–negative (ER-negative) breast cancers, a highly aggressive form of the disease, is extremely poor. For patients who are diagnosed with triple receptor–negative breast cancer (TNBC), the survival outlook is bleak. In hopes of finding a way to increase survival rates in TNBC patients, scientists are looking for molecular targets that could lead to effective drug therapies for these patients.
In this Study
The researchers’ primary aim was to identify molecular targets that are capable of suppressing tumorigenesis in TNBCs. To do this, they worked with breast cancer cell lines and mouse models to investigate the effect of inhibiting DAPK1, a protein associated with molecular pathways leading to cell death, in these experimental models. What they found was that the when DAPK1 is blocked it significantly decreases the tumor growth rate in TP53-mutant cells, but had no impact on the normal TP53 cells.
In addition to the laboratory assessment of inhibiting DAPK1, the researchers also completed a medical records evaluation of numerous breast cancer patient data sets and found that high DAPK1 expression associates with worse outcomes in individuals with p53-mutant cancers.
In a University press release about the study, Dr. Powel Brown, MD, PhD, professor and chair, Clinical Cancer Prevention, MD Anderson CC, and senior study author, stated, “This is a little studied kinase that has not been previously focused on for the treatment of cancer. We discovered a yin and yang phenomenon in terms of DAPK1 function. In normal cells this protein functions as a death inducer, but in TP53 mutant cells DAPK1 acts a critical driver of cancer cell growth.”
Dr. Brown continued, “While a new treatment for triple-negative breast cancers would be a major advance, DAPK1 inhibitors have the potential to be used to treat many different kinds of cancers with TP53 mutations, which include the most lethal cancers without effective treatments.”
Dr. Brown’s lab is presently working on ways to translate these findings into potential therapies using DAPK1 inhibitors, as well as, testing DAPK1 inhibition in combination with various types of chemotherapy to assess if there are any additional benefits that may lead to greater treatment efficacy.