Title |
Development of treatment strategies for advanced neuroblastoma
|
---|---|
Published in |
International Journal of Clinical Oncology, May 2012
|
DOI | 10.1007/s10147-012-0417-5 |
Pubmed ID | |
Authors |
Junichi Hara |
Abstract |
Neuroblastoma is the most common cancer in childhood. The majority of patients with neuroblastoma are assigned to the high-risk group based on age at diagnosis, stage, histology, MYCN status, and DNA ploidy. Their prognosis remains unsatisfactory; the 5-year event-free survival (EFS) rate is generally 40 %. During the past 20 years, much effort has been made to reinforce chemotherapy, including the introduction of high-dose chemotherapy with autologous stem cell rescue, resulting in a 5-year EFS rate of around 30 %. Subsequently, maintenance therapy aimed at eradicating residual tumors after induction and consolidation therapies was introduced, consisting of differentiation-inducing agents, retinoids, and immunotherapy using anti-GD2 antibodies combined with cytokines. However, such additional treatment provided benefit to only 10-20 % of patients, while the prognosis of about half the patients remains poor. Currently, novel targeted agents are under development. Among them, anaplastic lymphoma kinase (ALK) inhibitors and aurora kinase A inhibitors are promising. ALK somatic mutation or gene amplification predisposing neuroblastoma development occurs in up to 15 % of neuroblastomas. Crizotinib is a dual-specific inhibitor of ALK/Met and inhibits proliferation of neuroblastoma cells harboring R1275Q-mutated ALK or amplified wild-type ALK, but not cells harboring F1174L. Instead, cells with F1174L are sensitive to another small molecule ALK inhibitor, TAE684. Aurora kinase A plays a pivotal role in centrosome maturation and spindle formation during mitosis. MLN8237 (alisertib) is a small molecule inhibitor of aurora kinase A that is currently in early-phase clinical testing. Future treatment will be individually planned, adapting targeted agents based on personal biological tumor characteristics. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Czechia | 1 | 2% |
Austria | 1 | 2% |
Unknown | 63 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 12 | 18% |
Researcher | 11 | 17% |
Student > Master | 11 | 17% |
Other | 6 | 9% |
Student > Postgraduate | 4 | 6% |
Other | 9 | 14% |
Unknown | 12 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 14 | 22% |
Medicine and Dentistry | 14 | 22% |
Agricultural and Biological Sciences | 13 | 20% |
Neuroscience | 3 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
Other | 7 | 11% |
Unknown | 12 | 18% |