Baylor College of Medicine discovers new target for triple-negative breast cancer: MAPK4

Approximately 15-20% of breast cancers are triple-negative breast cancer (TNBC), a subtype that progresses rapidly, has a poor prognosis, and has limited treatment options

Through analysis of publicly available genomic datasets, the researchers found that a significant proportion of TNBC patients expressed significant levels of MAPK4

"This work combines two longstanding interests of our lab: studying the role of MAPK4 in human cancer and better understanding breast cancer, which is a comprehensive The most common cancer in the world

The researchers first analyzed the gene expression profiles of 817 human breast cancers in the Cancer Genome Atlas dataset, including various breast cancer subtypes

In addition, the team analyzed MAPK4 expression in breast cancer patient-derived xenografts (PDX), mostly with triple-negative breast cancer

"Previous research in our lab has shown that MAPK4 can play a cancer-promoting role in other types of cancer, such as prostate cancer," Yang said

The researchers also manipulated the expression levels of the MAPK4 gene in seven different human TNBC cell lines, some expressing higher levels of MAPK4 and others at lower levels

Yang and colleagues then delved into the mechanism by which MAPK4 promotes cancer development

Triple-negative breast cancer can activate AKT through two independent mechanisms: one mediated by MAPK4 and the other by PI3K

To confirm this idea, the researchers found that after knocking down MAPK4, cells became sensitive to PI3K inhibitors and reduced cancer growth

"Taken together, our findings based on MAPK4 expression provide a new opportunity for triple-negative breast cancer treatment, perhaps with a combination of inhibitors to control cancer growth," Yang said

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Wang, W.