Hypoxia

Hypoxia in Chordoma

A common characteristic of solid tumors like chordoma is that their cells are deprived of oxygen and must therefore adapt to the conditions in order to survive and proliferate.¹ The series of adaptations not only helps tumor cells to survive but also makes them more resistant to the effects of chemotherapy and radiation.²

Agents that interfere with the pathways involved in a tumor cell’s adaptive response to hypoxia, or agents that directly target hypoxic regions, could have anti-tumor effects and improve patient response to conventional therapies. There is evidence that pathways involved in cellular responses to hypoxia are upregulated in chordoma cells, and those pathways are being explored as targets for systemic therapies. Chordoma patients are currently enrolled in a number of clinical trials evaluating whether treatments can be directed at hypoxic chordoma cells, leaving normal tissues unharmed.

• Molecular Evidence
• Preclinical Evidence

Molecular Evidence

Protein Expression

• Expression of the proteins VEGF and HIF-1α are shown to increase in response to hypoxia. Levels of these proteins are increased in some chordomas, and both are being explored as promising targets for systemic therapies.³

Preclinical Evidence

In-Vitro Efficacy

• Evidence suggests that chordoma tumor cells adapt to hypoxic conditions; chordoma cell lines that initially grow in hypoxic conditions are later able to survive in hypoxic or in normal conditions.⁴
• Chordoma cells cultured under hypoxic conditions had increased proliferation, VEGF and HIF-1a expression compared to cells in normoxic conditions.⁵