Drugs in early clinical development for the treatment of osteosarcoma

ABSTRACT

Introduction: Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients.

Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development.

Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma.

KEYWORDS:

• Clinical trials
• immunotherapy
• macrophages
• microenvironment
• osteosarcoma
• immunomodulation
• cancer-initiating cells

Article highlights

• Tumour microenvironment is a key modulator in osteosarcoma development and is the source of new therapeutic targets

• Immunomodulators are promising drugs for controlling refractory and recurrent osteosarcoma (e.g. anti-GD2 therapy)

• Bone cells and bone matrix are two potential new targets for osteosarcoma (e.g. the anti-RANKL antibody, radium-223)

• Nanomedicine has led to the development of a new generation of compounds from ‘old’ drugs (e.g. Nab-paclitaxel)

• Large biological cohorts with relevant clinical annotations are essential for rare tumours and will be an important source of new therapeutic targets

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This study was supported by the Ligue Contre le Cancer, FR (research project: Equipe LIGUE 2012) and the Bone Cancer Research Trust, UK (research project number 144681).