Skin cancers constitute arguably the most common and increasingly prevalent human neoplasms. In United States alone, it is estimated that 76,400 patients will develop melanoma and 10,100 will die from the disease [1]. Several risk factors, ultraviolet light the most important of these, but also environmental carcinogens, contribute to the increasing incidence of skin cancers, especially among light-skinned individuals [2]. The most common human skin cancers are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but the most serious and most often fatal are malignant melanoma (MM) and Merkel cell carcinoma (MCC) [3].
Basal cell carcinomas arise in keratinocyte stem cells [5]. Usually, in BCCs, the hedgehog signaling pathway is activated causing neoplastic transformation of keratinocytes. Signaling by smoothened, via the cognate receptors, activates the hedgehog signaling pathway and has been implicated in BCC pathogenesis [6].
The most common treatment for BCC is surgical excision, nowadays using Mohs micrographic surgery to ensure complete excision while sparing the surrounding tissue [4]. Curettage, cryotherapy or laser ablation is sometimes used for lesions considered less risky.
The appearance of SSCs is variable, and it may present as an ulcer, lump or red patch on the skin, often with scaling or crusting. It is common in elderly. Actinic or solar keratosis, caused by exposure to UV light, is a premalignant lesion, a risk factor potentially leading to progression to invasive SCC. SCCs starting within actinic keratosis are generally low risk, with a more favorable prognosis [7].
Squamous cell carcinoma is usually surgically excised, using Mohs micrographic surgery, with chemotherapy including cisplatin or 5-fluorouracil less common [4]. Actinic keratoses may be treated as a prevention modality for SCC.
Melanoma is a malignant neoplasm of melanocytes, not keratinocytes. The main risk factor is UV light, especially UV-B, and both occasional severe sunburn and chronic sun exposure have been associated with MM formation [13]. People who burn easily, with light skin, blue eyes, red hair and freckles are at increased risk of MM. Giant congenital melanocytic nevi present a high risk, although MM can arise within pre-existing benign melanotic nevi or in normal appearing skin. MM can appear at any site, on skin as well as on oral, genital, urinary or ocular epithelial surfaces.
Population is urged to use the ABCDE rule when ascertaining the presence of MM [14]. These stand for A—asymmetry of the lesion, B—border (irregular), C—color (non-uniform), D—diameter (>6 mm, size of a pencil eraser) and E—evolving (changing in size, shape, color etc.). These features should raise apprehension of MM.
Wide local excision of the area of diagnosis is required. A sentinel lymph node biopsy is performed often, and whole body CT and PET scan are used occasionally in search for metastases. Conventional chemotherapy generally does not work. Recent research into mutations associated with MM identified BRAF gene as frequently mutated [15]; this led to development of specific inhibitors of the corresponding signal transduction pathways such as Vemurafenib, specifically targeting a recurrent mutation in BRAF, or Imatinib, a more general tyrosine kinase inhibitor [16]. Ipilimumab, a monoclonal antibody blocking CTLA-4, enhances immunotherapy against MM. Prognosis depends very much on the stage at which the tumor is detected.
In this volume, most chapters, understandably, deal with melanoma, the deadliest of skin cancers, and in particular with the cell surface proteins, potential melanoma markers [17].
In conclusion, this volume presents various aspects of human skin cancers, their mechanisms of formation, potential biomarkers and therapeutic targets, a component of the large worldwide effort to combat and eradicate this growing health concern.
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