An update on current and future treatment options for chondrosarcoma

ABSTRACT

Introduction: Human chondrosarcomas (CS; a malignant cartilage-forming bone tumor) respond poorly to chemotherapy and radiation treatment, resulting in high morbidity and mortality rates. Expanded treatment options are urgently needed.

Areas covered: This article updates our 2014 review, in which we evaluated the CS treatments available at that time and potential treatment options under investigation. Since then, advances in research findings, particularly from Chinese herbal medicines, may be bringing us closer to more effective therapies for CS. In particular, promising findings have been reported from research targeting platelet-derived growth factor receptor.

Expert opinion: Few treatment options exist for CS; chemotherapy is not even an option for unresectable disease, in which 5-year survival rates are just 2%. New information about the multitude of genes and signaling pathways that encourage CS growth, invasion and metastasis are clarifying how certain signaling pathways and plant-derived active compounds, especially molecularly-targeted therapies that inhibit the PDGF receptor, interfering with these biological processes. This review summarizes discoveries from the last 5 years and discusses how these findings are fueling ongoing work into effectively dealing with the disease process and improving the treatment of CS.

KEYWORDS:

• Chondrosarcoma
• cytogenetics
• herbal medicines
• treatment
• PDGFR

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.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are conducting a trial of an IDH inhibitor for Forma Therapeutics, and has served as a consultant for Adaptimmune, Blueprint, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immunedesign, Lilly, Merck, and Pharmamar. Peer reviewers have no other relevant financial relationships or otherwise to disclose.

Article highlights

• Current treatments for CS tumors have very limited therapeutic efficacy. Surgery is the mainstay of treatment, with complete, wide surgical excision of the CS preferred if feasible. Radiation therapy and chemotherapy are generally only beneficial as adjuvant or palliative treatments. Thus, CS is associated with considerable morbidity and low 5-year survival rates.

• A growing number of in vitro and preclinical investigations into natural plant-based products, including various well-known Chinese herbs, have revealed promising anti-CS properties, which will, hopefully, successfully translate into clinical studies.

• Molecularly-targeted therapies look particularly interesting, with research revealing novel biomarkers and potential therapeutic targets for CS angiogenesis and metastasis.

• Since 2014, the majority of research investigating the effects of adipokines (see Section 4) and other growth factors (see Section 5) has been performed by our laboratory. We have also summarized work performed in these research areas by other scientists.

Additional information

Funding

This work was supported by a grant from China Medical University (CMU 108-ASIA-06), and the Chinese Medicine Research Center, China Medical University, from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project funded by the Ministry of Education (MOE) in Taiwan (CMRC-CHM-3-1).