Dismutase mimetics and future of cancer therapy

Our research and that of others have shown that normal cells and cancer cells have differing sensitivities to superoxide and hydrogen peroxide. Harnessing that fundamental difference offers a truly new way to treat cancer while also reducing the toxicity of cancer therapy for the patient.

Targeting cancer cells with dismutase mimetics

Unlike normal cells, cancer cells and tumors are known to thrive with at least moderate elevations in superoxide.1 However, they generally have lower ability to dispose of hydrogen peroxide to oxygen and water. For this and other reasons, cancer cells are highly sensitive to hydrogen peroxide. As a result, increased levels of hydrogen peroxide are generated when dismutase activity is increased with our dismutase mimetics, selectively killing cancer cells while sparing normal cells.

In settings where superoxide levels are even further elevated in tumors, our dismutase mimetics can produce even greater differences, with increased cancer cell killing and actual protection of normal cells from superoxide-generated damage.

Dismutase mimetics and radiation treatment of cancer

Research suggests that our dismutase mimetics can increase the tumor-killing effects of radiation. These experiments also support the idea that this enhanced anticancer effect increases with the size of each radiation dose.

Radiation therapy is typically divided into a series of doses, or “fractions,” spread out over a period of days or weeks. As the size of each radiation fraction dose increases, the amount of superoxide generated also increases, and our dismutase mimetics can convert this into a cancer-killing increase in hydrogen peroxide. Emerging experimental data show that GC4419 significantly increases the anticancer effects of larger radiation fractions in tumor models. A common modality that uses precisely targeted, high-intensity radiation treatment is stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiation therapy (SABR).

Reference:
1. López-Lázaro M. Dual role of hydrogen peroxide in cancer: possible relevance to cancer chemoprevention and therapy. Cancer Lett. 2007;252(1):1-8.