Boosting retinoid activity

Researchers at Dartmouth Medical School in the USA have uncovered a potentially larger role for retinoids, compounds derived from vitamin A, in the treatment of cancer.

They found that the removal of a cell protein called RIP140 significantly enhances the cancer treatment and prevention abilities of retinoids in a laboratory setting.

The new study, published in the Journal of Biological Chemistry, builds on prior DMS research which showed that RIP140, a candidate retinoid receptor inhibitory protein, is a byproduct of one of these target genes. Now the research team has found that RIP140 is responsible for repressing retinoid receptors, adversely affecting the ability of retinoids to differentiate cancer cells and slow tumour growth in experiments using testicular cancer cells.

"Once RIP140 was removed, growth of cancer cells was repressed by retinoids at a faster rate compared to experiments where RIP140 was present,"​ said the researchers.

Retinoids have been known to have anti-tumour properties in the clinical setting. Based on laboratory findings, retinoids have the potential to treat and prevent a variety of leukaemia and solid cancers, primarily by causing cancers to differentiate.

This strategy may have less severe side-affects compared to conventional chemotherapy and may be a particularly valuable strategy in preventing cancer in high-risk individuals, note the researchers. However, thus far retinoids have only proven to be useful toward a small subset of cancer types in people.

"We were surprised at how much better retinoids worked in RIP140-free cells,"​ said Michael Spinella, assistant professor of pharmacology and toxicology of DMS' Norris Cotton Cancer Centre. "When we knocked RIP140 out of the cancer cells, they began to differentiate within two days; it usually takes five days to see any change in the cells."​

The team is hoping to ultimately use these findings to develop better differentiation-based strategies for the treatment of human cancer.