New enzyme drug target for WT1 oncogene in treating cancer

Research lead

Researchers at Manchester University have discovered that the enzyme HtrA2 can rid cells of the oncogene WT1, which is believed to be responsible for a wide range of cancers. WT1 is found at high levels in many leukaemias and solid cancers such as breast and lung cancer. The researchers Jorg Hartkamp and Stefan Roberts say this will provide a new target for developing drugs to treat cancers in which WT1 expression is elevated.

While WT1 is a well-known factor in cancer, having been discovered 20 years ago, it is claimed that this study, funded by the Wellcome Trust, Cancer Research UK and the Association of International Cancer Research, is the first to identify the enzyme that can break it down.

Hartkamp said the research involved studying a regulatory domain of WT1 to see what modified its activity. “We carried out a fishing experiment and discovered the role of the protease HtrA2 instead, by accident. This discovery has a much bigger impact.”

The researchers say HrtA2 may have even more targets beyond leukaemia, since it is unlikely that the protease cleaves only one transcription factor such as WT1.

The team plans to study HtrA2 further, to find out how it is inactivated in cancer cells, allowing WT1 to proliferate, and what other targets HtrA2 has, informing drug discovery.