The overall goal is to exploit an exciting new observation that a soccer ball-shaped cluster of 60 carbon atoms (a fullerene), which is similar to the soot in a chimney that is completely insoluble in water, can be made exquisitely water-soluble by decorating the surface with 6 pairs of custom-synthesized antennae-like extensions. Endowed with water-solubility, this construct that we call C60-ser, scavenges up free radicals generated in normal tissues by radiation therapy (RT) and thereby protects normal organs from collateral damage during cancer treatment. Importantly, this scavenging action does not hinder the effectiveness of RT in killing the cancer. One can imagine a scenario where add...

Read More

The overall goal is to exploit an exciting new observation that a soccer ball-shaped cluster of 60 carbon atoms (a fullerene), which is similar to the soot in a chimney that is completely insoluble in water, can be made exquisitely water-soluble by decorating the surface with 6 pairs of custom-synthesized antennae-like extensions. Endowed with water-solubility, this construct that we call C60-ser, scavenges up free radicals generated in normal tissues by radiation therapy (RT) and thereby protects normal organs from collateral damage during cancer treatment. Importantly, this scavenging action does not hinder the effectiveness of RT in killing the cancer. One can imagine a scenario where adding C60-ser to RT reduces treatment side-effects or a more provocative scenario where adding C60-ser allows us to escalate the RT dose to the cancer without increasing side-effects. As an exemplar of the latter approach, we consider pancreatic cancer, a cancer that is relatively resistant to RT with regular doses; but recent evidence from our group and others suggests that giving substantially higher radiation doses significantly improves patient survival. To date, the only way to give these high doses has been to use sophisticated technologies that are not widely available worldwide and/or to exclude patients with cancers close to the intestines (over two-thirds of all patients) because the intestines are very sensitive to RT. In principle, C60-ser given with RT could extend our reach to all these patients. This proposal, therefore, aims to continue investigating (i) how C60-ser protects normal cells without protecting the cancer, (ii) the optimal approach to combining C60-ser with RT, and (iii) how high a dose of RT can be safely given to a mouse model of pancreatic cancer to cure the cancer without side-effects. If successful, this strategy but could apply to any tumors in the abdomen or pelvis where the fear of intestinal toxicity causes us to give insufficient doses of RT.

Read Less