Enhancing non-small cell lung cancer therapy with superoxide dismutase mimetics and pharmacological ascorbate

Lung cancer is the leading cause of cancer related deaths. Research in treatment has led to developments in chemotherapy and radiation, often increasing survival times for patients and sometimes even cures. However, these advancements come with drawbacks as the very tools of treatment can cause damage to non-cancer tissue, leading to reduced quality of life in patients following therapy. Therefore, efforts to improve therapy going forward must focus not only on further improving current therapies, but also protecting normal tissue. To this end, we have employed small molecules that take advantage of fundamental differences between cancer and normal cell oxidative metabolism.

Superoxide dismutase (SOD) mimetics and pharmacological ascorbate (P-AscH‾) are examples of redox active agents. These drugs have been found to not only increase the efficacy of traditional therapy, but also protect normal tissue, through similar mechanisms. This work demonstrates that selective superoxide dismutase mimetics exhibit remarkable protective effects against the toxicity of cisplatin, a common chemotherapeutic agent used in lung cancer therapy, in kidneys of older rodents in two models of cisplatin induced kidney disease. We further show that SOD mimetics are protective against toxicity induced by radiation that is targeted to the heart. Finally, we demonstrate the by combining SOD mimetics and P-AscH‾, we can improve the effects of radiation and chemotherapy on lung cancer cells themselves, in both in vitro and in rodent models. This work provides evidence that redox based drugs, namely SOD mimetics and P-AscH‾, could be powerful tools in the treatment of lung cancer.