There is a possibility that targeting the enzyme MAPK4 in human prostate cancer might provide a novel therapeutic strategy for the disease, said researchers.

The study indicates that the enzyme MAPK4 concertedly activates androgen receptor (AR) and AKT, molecules at the core of two cellular signalling pathways known to promote prostate cancer growth and resistance to standard therapy. "Our findings suggest the possibility that regulating MAPK4 activity could result in a novel therapeutic approach for prostate cancer," said researcher Feng Yang, Assistant Professor at Baylor College of Medicine in the US. "We are interested in finding an inhibitor of MAPK4 activity that could help better treat prostate cancer and other types of cancers in the future," Yang added.

In their previous study, the researchers discovered that MAPK4 could trigger the AKT pathway, not only in prostate cancer but in other cancers as well, such as lung and colon cancers. In the current study published in the 'Journal of Clinical Investigation', the researchers found that MAPK4 also activates the AR signalling pathway by enhancing the production and stabilisation of GATA2, a factor that is crucial for the synthesis and activation of AR.

Further experiments showed that MAPK4 triggered the concerted activation of both AR and AKT pathways by independent mechanisms, and this promoted prostate cancer growth and resistance to castration therapy, a standard medical treatment for advanced/metastatic prostate cancer. Importantly, genetically knocking down MAPK4 reduced the activation of both AR and AKT pathways and inhibited the growth, including castration-resistant growth, of prostate cancer in animal models. The researchers anticipate that knocking down MAPK4 could also reduce the growth of other cancer types in which MAPK4 is involved.