Cancers do not arise solely from a single deregulated group of cells but rather as a combined result of various alterations in organ and tissue homeostasis. In fact, many genetic changes found in invasive and metastatic tumors are also found in apparently normal tissues and, for reasons that are not yet understood, only a minor fraction of pre-malignant lesions progress to malignancy.
A main research focus at ICPI is on biological determinants of pre-malignant to malignant skin tumor conversion and on field cancerization, a process of major clinical significance that consists of multifocal and recurrent tumors that are associated with widespread changes of surrounding normal tissues (Dotto, 2014).
The 3 main types of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma have a major impact on human health, with skin BCC and SCC being by far the most common type of human cancer worldwide, and melanoma being among the most aggressive. While SCCs and melanomas are preceded and accompanied by premalignant lesions, BCCs appear without discernible precursors but also frequently appear as multiple or recurrent lesions.
Skin field cancerization is a major clinical problem for sun-exposed ageing human populations of caucasian origin and for organ transplant recipient patients under treatment with immune suppressants to prevent rejection.
While previous research on field cancerization has focused on changes in cancer cells of origin as primary drivers, work at ICPI has pioneered studies on the initiating role that stromal fibroblast alterations can also play in the whole process, with modulation of androgen receptor expression and activity as a key player (Clocchiatti et al., 2018).
Overall, a complex interplay involves differences in sex hormones levels and activity in the mesenchymal versus epithelial compartment of the skin, as a function of sex, age, and UV sun exposure. Insights into underlying cellular and molecular mechanisms are of likely translational significance for devising novel approaches for primary, secondary and tertiary cancer prevention targeting the epigenome.