Unveiling Spontaneous Regression of Neuroblastoma and its Application to the Therapy

Japanese

Laboratory of Innovative Cancer Therapeutics

(Leader: Akira NAKAGAWARA, MD, PhD)

Summary of research:

Neuroblastoma is one of the typical children's solid tumors and originate from adrenal medulla and sympathetic ganglia. The tumors occurred in infants under one year of age often regress spontaneously even though there are metastases to liver, skin and bone marrow, On the other hand, those in older patients are usually aggressive and reluctant to any therapy.

We have previously discovered that expression of TrkA receptor may be the key to regulate the spontaneous regression, and that the relative deficiency of its ligand, NGF, may lead the tumor cells to die. In addition, we hypothesized that the events to block the regression may make the tumor cells more aggressive.

We have so far identified many important genes regulating regression, differentiation and growth of neuroblastoma, most of which could be targets for therapy. Recently, we have also identified the ALK gene mutated in primary neuroblastomas.

Keywords:

Neuroblastoma, Spontaneous regression, TrkA, NGF, ALK, Programmed cell death

Recent main publications:

• Chen Y et al.  Nature 2008; 455: 971-974
• Munirajan AK et al.  J Biol Chem 2008; 283:24426-24434
• Tomioka N et al. Oncogene 2008; 27: 441-449
• Nakanishi M et al. J Biol Chem 2007; 282:22993-23004
• Furuya K et al. J Biol Chem 2007; 282:18365-18378
• Aoyama M et al.  Cancer Res 2005; 65: 4587-4597
• Ohira M et al.  Cancer Cell, 2005; 7: 337-350.