Unearthing the road to resistance

Standard treatment for adult T cell leukemia (ATL), a lymphoid malignancy related to retrovirus HTLV-1, includes administration of glucocorticoid drugs. But many patients become resistant to this therapy, and experience cancer relapse. Now, a research team led by Junji Yodoi of Kyoto University, Japan, has revealed that the development of glucocorticoid resistance is linked to a drop in the levels of the protein thioredoxin-binding protein-2 (TBP-2)¹.

In cell culture experiments, the team found that leukemic cells from ATL patients could initiate cell death activation in response to glucocorticoids. However, a subpopulation of these cells soon became resistant to the drugs, and these resistant cells seemed to lose expression of both the glucocorticoid receptor and TBP-2.

In the cell population that usually would die in response to glucocorticoids, the researchers found that preventing expression of TBP-2 could block the cancer-killing effects of the glucocorticoid drugs. They also observed that in the cells normally resistant to glucocorticoids, increasing the expression of TBP-2 could cause their death. Further, a chemical that could induce the expression of TBP-2 could also render glucocorticoid-resistant cells sensitive to the drugs.

The researchers therefore conclude that targeting TBP-2 could be a potential therapeutic approach to treating cancer patients that have become resistant to glucocorticoid drugs.