scholarly journals Oh, the Mutations You’ll Acquire! A Systematic Overview of Cutaneous Squamous Cell Carcinoma

2021 ◽  
Vol 55 (S2) ◽  
pp. 89-119
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Sun Exposure ◽  
The United States ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Targeted Therapeutics ◽  
Invasion And Metastasis ◽  
Mutational Burden ◽  
Significant Mortality

Nearly two million cases of cutaneous squamous cell carcinoma (cSCC) are diagnosed every year in the United States alone. cSCC is notable for both its prevalence and its propensity for invasion and metastasis. For many patients, surgery is curative. However, patients experiencing immunosuppression or recurrent, advanced, and metastatic disease still face limited therapeutic options and significant mortality. cSCC forms after decades of sun exposure and possesses the highest known mutation rate of all cancers. This mutational burden complicates efforts to identify the primary factors driving cSCC initiation and progression, which in turn hinders the development of targeted therapeutics. In this review, we summarize the mutations and alterations that have been observed in patients’ cSCC tumors, affecting signaling pathways, transcriptional regulators, and the microenvironment. We also highlight novel therapeutic opportunities in development and clinical trials.

Schutz vor Hautkrebs durch Vitamin-A-reiche Ernährung?

2020 ◽  
Vol 52 (01) ◽  
pp. 25-28
Keyword(s):  
United States ◽  
Squamous Cell Carcinoma ◽  
Vitamin A ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
The United States ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Carcinoma Risk

Kim J, Park MK, Li WQ et al. Association of vitamin A intake with cutaneous squamous cell carcinoma risk in the United States. JAMA Dermatol 2019; doi:10.1001/jamadermatol. 2019.1937

scholarly journals Molecular Approach to Cutaneous Squamous Cell Carcinoma: From Pathways to Therapy

2020 ◽  
Vol 21 (4) ◽  
pp. 1211
Author(s):  
Elisabetta Palazzo ◽  
Maria I. Morasso ◽  
Carlo Pincelli
Keyword(s):  
United States ◽  
Squamous Cell Carcinoma ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
The United States ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Molecular Approach

Cutaneous squamous cell carcinoma (cSCC) represents the second most frequent skin cancer, recently showing a rapid increase in incidence worldwide, with around >1 million cases/year in the United States and 2500 deaths [...]

scholarly journals Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine Model of Cutaneous Squamous Cell Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Erin M. Burns ◽  
Kathleen L. Tober ◽  
Judith A. Riggenbach ◽  
Donna F. Kusewitt ◽  
Gregory S. Young ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Sun Exposure ◽  
Epidemiological Studies ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Exposure Model ◽  
Uvb Exposure

Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive.

Association of tumor mutational burden in cutaneous squamous cell carcinoma with genomic alterations in Notch family receptors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13031-e13031
Author(s):  
Eric Allan Severson ◽  
Shakti Ramkissoon ◽  
Sugganth Daniel ◽  
Jo-Anne Vergilio ◽  
Laurie M. Gay ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Family Member ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Genomic Alterations ◽  
Functional Impact ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Frameshift Indels

e13031 Background: In Cutaneous Squamous Cell Carcinoma (cSqCC), Notch1, Notch2, and Notch3 have been identified as tumor suppressors with a high rate of inactivating mutations early in cSqCC pathogenesis. Despite the high frequency of alterations, the biologic and therapeutic implications of Notch genomic alterations (GAs) in cSqCC are incompletely understood. Methods: 232 FFPE samples of cSqCC were evaluated by comprehensive genomic profiling (CGP) of 315 genes and analyzed for all classes of GAs, with diagnoses confirmed by central pathology review. Notch GAs with unknown functional impact were excluded. Tumor mutational burden (TMB) was calculated from 1.11 Mb of sequenced DNA and reported as mutations/Mb. Results: The cohort of 232 samples was 78% male and 22% female, aged from 17 to 88, with confirmed metastatic disease in 32% of cases. 115 (50%) samples had a Notch family member GA with a known or predicted functional impact. 96 cases had Notch1 GAs, 43 cases had Notch2 GAs, and 14 cases had Notch3 GAs with 40 cases having GAs in multiple Notch family members. These mutations were 41% missense, 34% nonsense, 15% splice site, 9% frameshift indels, and 1% non-frameshift indels alterations. Patients with Notch GAs were significantly older (median 70 years old vs median 64, p < 0.01). TMB was increased among samples with Notch GAs (median TMB of 63 mutations/mb versus 20 mutations/mb, p < 1x10-6), with similar differences for primary and metastatic samples. Cases with Notch GAs had more total GAs per case (mean 10.4 vs 7.4, p < 1.5x10-10); however, the top co-mutated genes were the same (TP53, CDKN2A, FAT1, MLL2). Both groups had a high proportion of C- > T/G- > A transitions, consistent with UV damage; however, the proportion was higher in cases with Notch GAs (median 83% vs 80%) - a difference seen in primary and metastatic samples. Conclusions: 50% of cSqCC cases had a Notch family member loss of function GA, which was associated with increased TMB in the primary and metastatic setting. With pre-clinical models and case studies showing responses to PD-1 inhibitors in cSqCC, further investigations are warranted into the associations of Notch GAs with mutational burden and response to immunotherapy.

scholarly journals Prospective Study of Human Polyomaviruses and Risk of Cutaneous Squamous Cell Carcinoma in the United States

2016 ◽  
Vol 25 (5) ◽  
pp. 736-744 ◽  
Author(s):  
Anala Gossai ◽  
Tim Waterboer ◽  
Heather H. Nelson ◽  
Jennifer A. Doherty ◽  
Angelika Michel ◽  
...  
Keyword(s):  
United States ◽  
Squamous Cell Carcinoma ◽  
Prospective Study ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
The United States ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Human Polyomaviruses

scholarly journals Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

2020 ◽  
Vol 21 (8) ◽  
pp. 2956 ◽  
Author(s):  
Roberto Corchado-Cobos ◽  
Natalia García-Sancha ◽  
Rogelio González-Sarmiento ◽  
Jesús Pérez-Losada ◽  
Javier Cañueto
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Basis ◽  
Checkpoint Inhibitors ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Drug Induced ◽  
Mutational Burden ◽  
Therapeutic Landscape ◽  
Increased Risk

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise. Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic. The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape. This review focuses on the molecular basis of CSCC and the current biology-based approaches of targeted therapies and immune checkpoint inhibitors. Another purpose of this review is to explore the landscape of drugs that may induce or contribute to the development of CSCC. Beginning with the pathogenetic basis of these drug-induced CSCCs, we move on to consider potential therapeutic opportunities for overcoming this adverse effect.

scholarly journals Association of Vitamin A Intake With Cutaneous Squamous Cell Carcinoma Risk in the United States

2019 ◽  
Vol 155 (11) ◽  
pp. 1260 ◽  
Author(s):  
Jongwoo Kim ◽  
Min Kyung Park ◽  
Wen-Qing Li ◽  
Abrar A. Qureshi ◽  
Eunyoung Cho
Keyword(s):  
United States ◽  
Squamous Cell Carcinoma ◽  
Vitamin A ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
The United States ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Carcinoma Risk

scholarly journals Genetic ancestry, skin pigmentation, and the risk of cutaneous squamous cell carcinoma in Hispanic/Latino and non-Hispanic white populations

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Eric Jorgenson ◽  
Hélène Choquet ◽  
Jie Yin ◽  
Thomas J. Hoffmann ◽  
Yambazi Banda ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Skin Pigmentation ◽  
Sun Exposure ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Genetic Ancestry ◽  
European Ancestry ◽  
History Of ◽  
Hispanic Latinos

AbstractAlthough cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in individuals of European ancestry, the incidence of cSCC in Hispanic/Latinos is also increasing. cSCC has both a genetic and environmental etiology. Here, we examine the role of genetic ancestry, skin pigmentation, and sun exposure in Hispanic/Latinos and non-Hispanic whites on cSCC risk. We observe an increased cSCC risk with greater European ancestry (P = 1.27 × 10−42) within Hispanic/Latinos and with greater northern (P = 2.38 × 10−65) and western (P = 2.28 × 10−49) European ancestry within non-Hispanic whites. These associations are significantly, but not completely, attenuated after considering skin pigmentation-associated loci, history of actinic keratosis, and sun-protected versus sun-exposed anatomical sites. We also report an association of the well-known pigment variant Ala111Thr (rs1426654) at SLC24A5 with cSCC in Hispanic/Latinos. These findings demonstrate a strong correlation of northwestern European genetic ancestry with cSCC risk in both Hispanic/Latinos and non-Hispanic whites, largely but not entirely mediated through its impact on skin pigmentation.

Sign in / Sign up

Export Citation Format

Share Document