Introduction

As part of Novogen’s research into synthetic phenolic hormones and their biological activities, one compound, NV-07α, has emerged with profound anti-inflammatory and immunostimulatory properties. One development path for this compound has been in topical applications to protect from UV-induced skin damage, as an anti ageing formulation and to prevent the long term effects of UV-exposure including skin cancer development. As a result a family of compounds with potential for dermatological use has been synthesized.

NV-07α

NV-07 used topically has produced pronounced protection of mice against UV-induced inflammatory changes in the skin, and against UV-induced skin immune suppression. These effects translated into significantly reduced skin damage after acute UV-exposure, with potential to produce anti-ageing effects, but also reduced incidence and severity of skin cancers in mice chronically exposed to UV radiation or to known chemical carcinogens. Importantly, all of these effects were obtained by NV-07 application after UV-irradiation, indicating a repair process rather than a UV blocking effect. NV-07 is thus highly effective as an after-sun treatment to repair UV-induced skin damage and to prevent both induction and progression of malignant and non-malignant skin cancers, as well as chemically induced cancers. In view of the recent realisation that simple sun blocks do not afford protection against skin cancer, this new drug will address a major new therapeutic opportunity as a cosmetic anti-ageing product as ell as an important new development in the fight against skin cancer.

The case for improved UV-protection skin care

UV radiation causes sunburn and immunosuppression. While sunburn leads to premature skin ageing it also promotes biochemical changes in the skin promoting carcinogenesis. Whereas there are a large number of cosmetic products which prevent UV-induced skin damage by filtering out and/or absorbing the harmful irradiation wavelengths, these formulations are only effective if applied prior to UV exposure and generally are only able to prevent the erythema associated with UV damage (ie. sunburn). They generally have little impact on the now well-recognized and more sinister changes causing skin immunosuppression. It is now generally understood that while the inflammatory events following UV exposure may lead to structural damage to the skin, the skin immune deficit which also follows UV exposure has far more relevant health implications by reducing immune surveillance and allowing induction and progression of skin tumours. Other so-called “anti-ageing” creams usually contain emollients which temporarily moisturise and soften skin but without active ingredients which reverse UV damage.

The International Agency for Research on Cancer (IARC), part of the World Health Organisation, recently announced under the heading “Do sunscreens prevent skin cancer?” that “...for malignant melanoma, which is characterized by metastatic spread to other organs, often with fatal consequences, ...several relevant epidemiological studies have shown significantly higher risks for melanoma in users of sunscreens than in non-users.” In the text of the report on which this announcement was based it was noted that “Topical use of sunscreens reduces the risk for sunburn in humans. Sunscreens probably prevent squamous-cell carcinoma of the skin when used mainly during unintentional sun exposure. No conclusion can be drawn about the cancer-preventive activity of topical use of sunscreens against basal-cell carcinoma and cutaneous melanoma.” (Recommendations of an International Working Group of experts convened by the International Agency for Research on Cancer of the World Health Organization (WHO), in Lyon, France). Whether this is due to users allowing themselves to be exposed to greater levels of UV irradiation, in the belief that they are protected from its effects by sunscreen application, or whether there are carcinogenic processes against which existing sunscreens do not protect is not well understood. This heightens the need for additional therapeutic intervention to assist in the prevention and repair of UV-induced damage.