A huge challenge posed by any cancer is the danger of metastasis and possible resurgence following treatment. Recent work has identified the enzyme involved in cloning of cancer stem cells. These cells (CSCs) are tumourigenic – that is, they differentiate into tumour cells. The California-based team who identified the enzyme in question published their report online on Christmas Eve in Proceedings of the National Academy of Sciences.
The team were working on chronic myeloid leukaemia (CML), a cancer of the blood and marrow currently affecting 70,000 Americans. What is staggering is that estimates suggest that USA cases will almost triple by 2050. The rapid rise in cases of this cancer means that progress in understanding its pathway is encouraging. Even with the advent of more effective treatments (for example tyrosine kinase inhibitors) remission from cancers like CML is far from guaranteed. The self-renewing capacity of stem cells means that if some CSCs escape destruction the cancer may reoccur or spread. This relapse occurs in the majority of CML cases when treatment comes to an end.
Dr Catriona Jamieson and her international team of researchers established that levels of an enzyme called adenosine deaminase (ADAR1) increase during inflammation, a key component in cancer development. ADAR1 is translated during normal embryonic development. It is involved in blood cell development and is expressed during infections, when extra blood cells are required. In CML cases, ADAR1 is over-expressed and this causes CSC resilience even in the face of aggressive treatment. The mechanism of ADAR1-induced CSC self-renewal involves RNA missplicing. Jamieson’s previous work has emphasised the importance of RNA editing in cancer development, whereas the common emphasis has until recently been on DNA instability.
Having been implicated in CSC resistance, ADAR1 may provide a target in the process of CML treatment. The enzyme could be inhibited with a small-molecule inhibitor. Hence CSCs may lose their ADAR1-derived capacity for self-renewal; if this were the case, the cancer may be eradicated for good.
