Neuroblastoma therapy: what's in the pipeline?

Publication Type:

Journal Article

Source:

Endocr Relat Cancer, Volume 18, Number 6, p.R213-R231 (2011)

ISBN:

1479-6821 (Electronic)13

DOI Name (links to online publication)

10.1530/ERC-11-0251

Abstract:

Despite the expansion of knowledge about neuroblastoma (NB) in recent years, the therapeutic outcome for children with a high-risk NB has not improved significantly. Therefore, more effective therapies are needed. This might be achieved by aiming future efforts at recently proposed but not yet developed targets for NB therapy. In this review, we discuss recently proposed molecular targets that are in clinical trials and in particular, those that are not yet explored in the clinic. We focus on a selection of these molecular targets for which promising in vitro and in vivo results have been obtained by silencing/inhibiting them. In addition, these selected targets are involved at least in one of the NB tumorigenic processes: proliferation, anti-apoptosis, angiogenesis and/or metastasis. In particular, we will review a recently proposed target, the microtubule associated proteins (MAPs) encoded by doublecortin-like kinase gene (DCLK1). DCLK1-derived MAPs are crucial for proliferation and survival of neuroblasts and are highly expressed not only in NB but also in other tumours, such as gliomas. Additionally, we will discuss neuropeptide Y, its Y2 receptor and cathepsin L as examples of targets to decrease angiogenesis and metastasis of NB. Furthermore, we will review the microRNAs that have been proposed as therapeutic targets for NB. Detailed investigation of these not yet developed targets as well as exploration of multi-target approaches might be the key to a more effective NB therapy, i.e. increasing specificity, reducing toxicity and avoiding long-term side effects.

18/01/2013