Incidence, Mortality, and Trends of Nonmelanoma Skin Cancer in GermanyIncreasing incidence rates (IRs) of nonmelanoma skin cancer (NMSC) in white populations have been described worldwide. Cancer registry data from the Saarland and Schleswig-Holstein federal states were used to analyze incidence and mortality trends in Germany. Age-standardized rates were compared with crude rates to assess disease burden. Joinpoint regression models were used to estimate annual percentage changes and 95% confidence intervals, allowing us to assess temporal trends between 1970 and 2012.
Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell CarcinomaSunlight is the principal environmental risk factor for keratinocyte cancers, but other carcinogens have also been implicated, including tobacco smoke. Findings have been conflicting, however. We investigated associations between cigarette smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained through data linkage and verified by histopathology reports.
NADPH Oxidase-1 Plays a Key Role in Keratinocyte Responses to UV Radiation and UVB-Induced Skin CarcinogenesisThe nicotinamide adenine dinucleotide phosphate oxidase (NOX) family enzymes are involved in several physiological functions. However, their roles in keratinocyte responses to UV radiation have not been clearly elucidated. This study shows that, among other NOX family members, UVB irradiation results in a biphasic activation of NOX1 that plays a critical role in defining keratinocyte fate through the modulation of the DNA damage response network. Indeed, suppression of both bursts of UVB-induced NOX1 activation by using a specific peptide inhibitor of NOX1 (InhNOX1) is associated with increased nucleotide excision repair efficiency and reduction of apoptosis, which is finally translated into decreased photocarcinogenesis.
Cancer Stem Cells in Squamous Cell CarcinomaCancer stem cells (CSCs) are found in many cancer types, including squamous cell carcinoma (SCC). CSCs initiate cancer formation and are linked to metastasis and resistance to therapies. Studies have revealed that several distinct CSC populations coexist in SCC and that tumor initiation and metastatic potential of these populations can be uncoupled. Therefore, it is critical to understand CSC biology to develop novel CSC-targeted therapies for patients with SCC with poor prognoses. This review compares the properties of CSCs in SCC with normal stem cells in the skin, summarizes current advances and characteristics of CSCs, and considers the challenges for CSC-targeted treatment of SCC.
The Senescence-Associated Secretory Phenotype: Critical Effector in Skin Cancer and AgingCellular senescence, a state of stable cell cycle arrest in response to cellular stress, is an indispensable mechanism to counter tumorigenesis by halting the proliferation of damaged cells. However, through the secretion of an array of diverse cytokines, chemokines, growth factors, and proteases known as the senescence-associated secretory phenotype (SASP), senescent cells can paradoxically promote carcinogenesis. Consistent with this, removal of senescent cells delays the onset of cancer and prolongs lifespan in vivo, potentially in part through SASP reduction.
Prevalence of Skin Cancer and Related Skin Tumors in High-Risk Kidney and Liver Transplant Recipients in Queensland, AustraliaThe increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated.
Identification of Susceptibility Loci for Cutaneous Squamous Cell CarcinomaWe report a genome-wide association study of cutaneous squamous cell carcinoma conducted among non-Hispanic white members of the Kaiser Permanente Northern California health care system. The study includes a genome-wide screen of 61,457 members (6,891 cases and 54,566 controls) genotyped on the Affymetrix Axiom European array and a replication phase involving an independent set of 6,410 additional members (810 cases and 5,600 controls). Combined analysis of screening and replication phases identified 10 loci containing single-nucleotide polymorphisms (SNPs) with P-values < 5 × 10−8.
Sustained Akt Activity Is Required to Maintain Cell Viability in Seborrheic Keratosis, a Benign Epithelial TumorSeborrheic keratoses (SKs) are common benign skin tumors that share many morphological features with their malignant counterpart, squamous cell carcinoma. SKs frequently have acquired oncogenic mutations in the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt signaling cascade. We developed a reliable culture system to study SKs in vitro and screened these cells using a library of selective kinase inhibitors to evaluate effects on cell survival. These benign tumors are sensitive to inhibition by ATP-competitive Akt inhibitors, including A-443654 and GSK690693.