Targeting of Cytochrome CYP1B1 in the Treatment of Head and Neck and Lung cancers

(Ref. No. 243-MC)

Background

Exposure to tobacco smoke is a major risk factor for development of cancer and is estimated to account for approximately 90% of all lung cancers. Remarkably, women appear to have an increased susceptibility to tobacco carcinogens. Numerous other cases associated with tobacco smoke comprise Squamous Cell Carcinoma of Head and Neck (HNSCC), a heterogeneous group of tumors that develop primarily in the squamous epithelium of the lip, mouth, throat, nasal cavity, and paranasal sinuses. However, a moderate percentage of young female patients with HNSCC are non-smokers. Therefore, in addition to the main risk factors, female hormones can contribute to carcinogenesis associated with tobacco smoke and affect the susceptibility of women to lung cancer. Recently, lung cancer in women has surpassed breast cancer as the primary cause of cancer-related mortality and advanced methods of therapy are highly needed.

Summary of the Invention

Researchers from Fox Chase Cancer Center have observed that exposure to tobacco smoke causes changes in the expression of certain genes, and in the main, cytochrome CYP1B1. CYP1B1 is an enzyme that catalyzes the formation of carcinogenic metabolites of estrogens and certain chemical components of tobacco smoke that are subsequently inactivated by one or more detoxification enzymes. Consistent with induction of CYP1B1 and its role in estrogen metabolism, oxidation of estrogen was identified as part of the network significantly modulated by tobacco smoke exposure. Inhibition of the expression or biologic activity of CYP1B1 in premalignant or malignant cells causes subsequent inhibition of motility or proliferation of the cells. Such effect of down regulation of CYP1B1 itself or its substrate provide a novel target for cancer therapy and can prevent the invasion and metastasis as cancer develop and progress.

Publications

Meireles S.I. et al. Early changes in gene expression induced by tobacco smoke: Evidence for the importance of estrogen within lung tissue. Cancer Prev Res (Phila). 2010 Jun;3(6):707-17.