Molecular carcinogenesis for development of targeted therapy

Japanese

Division of Molecular Carcinogenesis

(Leader: Takehiko Kamijo, MD, PhD)

Summary of research:

Neuroblastoma (NB) is the most common extracranial solid malignant tumor in childhood. Although the survival of many childhood malignancies has been improved by recent therapies, high-risk neuroblastoma is still one of the most difficult tumors to cure, with only 30% long-term survival despite intensive multi-modal therapy. To improve the survival rate of NB, new treatments and a better understanding of drug resistance mechanisms have been required.

We have previously discovered that Doxo- and etoposide-induced cell death in NB is dependent on the p53 function and Noxa is one of the important effector of the p53-dependent apoptotic cell death (Oncogene, 2008). Now we are investigating molecular mechanism of wtp53 functional inactivation in NB.

Cancer stem cells (CSCs) are thought to be critical for initiation and propagation of many types of cancer. Because these cells are resistant to conventional therapies, they have been very difficult to eliminate. We are now studying the functions of cancer stem cell markers in several malignancies to conquer the CSCs in the resistant tumors.

Keywords:

Neuroblastoma, ARF/p16, p53 families, epigenetics, Cancer Stem cells, Polycombs

Recent main publications:

• Nakazawa Y et al. J Biol Chem 2003; 278:27888-95
• Miki J et al. Genes To Cells. 2007;12:1371-82.
• Kurata K et al. Oncogene 2008; 27:741-54
• Abe M K et al. Pediatric Int 2009; 51:103-6
• Komatsu S Oncogene,2009; 28:3631-41.
• Ochiai H et al. Oncogene 2010; in press.
• Iwata S et al. Cancer Sci 2010; in press.

Motivated students will be very welcome to join our research projects.