History of ANR: Advances in Neuroblastoma Research

See photos posted on the ANR site!  http://www.anr2010.com/photos/5166/Page.aspx

Dr Audrey Evans initiated this meeting in 1974, and interestingly, this was the same year she helped found the first Ronald McDonald House in Philadelphia. Approximately 50 researchers and clinicians participated in that first ANR meeting. There was one abstract submitted on genetics/genomics that year.

This meeting has 600+ registrants from 37 countries who submitted 500+ abstracts. Over 200 abstracts are on genetics or genomics. This is also the largest pediatric oncology meeting that Sweden has ever hosted. There are 4 Nobel prize winners participating here in the “home” of the prize.

This year is also the 200th anniversary of the prestigious Karolinska Institute, founded as a training course for military surgeons in 1810 and now one of the premiere medical research institutions in the world.

Update on ALK mutations and implications for treatment

The first day offered an update course on neuroblastoma as well as the welcome ceremonies. A significant focus was on genome wide association studies which describe the association of mutations with incidence of neuroblastoma, as well as potential prognostic information, cell origin,  and new targets. The technology is rapidly expanding to produce more data, and the cost is falling. Eventually the most expensive part will be the data handling. This technology is extremely important for the future of NB diagnosis and treatment. The landmark discoveries of the ALK mutation (and previously known PHOX2b mutation) from Dr Maris’ lab has provided strong evidence that neuroblastoma is not associated with environmental factors, but rather a “perfect storm” of genetic mutations. Since some of these mutations have functional implications, they can serve as targets for treatment, as in the case of the ALK inhibitor. As the mutations are further described, it may be possible to more accurately identify those intermediate risk cases that require more treatment, and the ultra-high risk cases that are likely to fail front- line therapy, allowing for new treatment strategies for that group.

Dr Yael Mosse presented the clinical relevance of ALK mutations, and elucidated the significance of hereditary features, target potential, and future possibilities. At this point they have found in familial NB cases ~80% have ALK mutations and ~10% have PHOX2B mutations. A variety of other genes will likely describe the remaining 10%.

Out of 1148 NB cases including all risk categories, 7.3% were found to have ALK mutation. But in older children (10 years old or older at diagnosis) the proportion is higher at 17%. To date over 20 ALK mutations have been discovered, but there are three “hot spots” and of those, R1275Q (~42%) and F1174L (~17%) are the most common.

In today’s plenary session Yael Mosse discussed “Exploitation of ALK as a therapeutic target in neuroblastoma” and explained that they found 11.5% of MYCN amplified tumors have ALK mutations, as well as 8.8% of all high risk.

The most significant and surprising issue is that after this mutation was discovered in NB, a drug happened to be already available to target this mutation (previously found in lung cancer). To date several NB children with ALK mutation have been enrolled on the trial and while it is too early to guess at the potential for responses, it is encouraging to know there is already an antibody suggested for use in overcoming any possible acquired resistance.