Objectives

Chondrosarcoma, a rare bone sarcoma arising from transformed chondrocytes, is treated primarily with surgical resection. For non-resectable chondrosarcomas chemo- and radiotherapy are largely ineffective for the most common subtypes of the disease, therefore new treatment options are urgently needed.

Clinical research in OS is hampered by a limited pipeline of new agents. Drug repurposing, an alternative development pathway that seeks to reuse existing drugs as the source of new treatment options, represents an interesting opportunity to solve this issue. The drug repurposing strategy utilises existing data on safety, dosing and clinical experience.

Our goal was to list existing drugs, including non-cancer drugs, active against chondrosarcoma to prioritize future research and trials.

Methods

We used the Repurposing Drugs in Oncology (ReDO) list of 255 approved non-cancer drugs. We queried PubMed for each drug and screened all abstracts to assess relevance, type of evidence (in vitro, in vivo, human data). A similar process was used to generate a database of PubMed abstracts for licensed cancer medications with any type of data in chondrosarcoma.

Results

From the 255 ReDO non-cancer drugs, 20 (8%) have evidence of activity against chondrosarcoma. Of these, 4 (2%) are supported by human data (marked with *).

Acetylsalicylic acid

Chloroquine *

Melatonin

Plerixafor

Alendronic Acid

Ciprofloxacin

Metformin

Simvastatin

Amiloride

Disulfiram

Midazolam

Sirolimus *

Caffeine *

Doxycycline

Omeprazole

Valproic Acid

Celecoxib

Esomeprazole

Pioglitazone

Zoledronic Acid *

Few of these repurposed agents show direct cytotoxic effects – mechanisms of action include potentiating the effects of chemotherapy agents and effects on the tumour microenvironment.

Additionally, a similar number of licensed cancer medications have some data (case reports, retrospective or clinical trial) of activity in chondrosarcoma, including: cyclophosphamide, imatinib, nivolumab, pazopanib, sunitinib and others.

Conclusions

A range of evidentiary sources indicate that a number of licensed non-cancer and cancer drugs have anti-chondrosarcoma activity. The level of evidence includes human data, including data from case reports, retrospective analyses and small clinical trials. Given that chondrosarcoma is generally accepted to be relatively resistant to standard cytotoxics investigation, pre-clinical and clinical, into the combination of non-cancer and cancer drugs is warranted.