Pathogenesis Of Basal Cell Carcinoma Research Articles

Understanding and managing locally advanced basal cell carcinoma: insights into pathogenesis, therapeutic strategies, and the role of hedgehog pathway inhibitors.

Understanding and managing locally advanced basal cell carcinoma (BCC) is crucial given its substantial prevalence and potential for local tissue destruction. While BCC typically exhibits low metastatic potential, its high incidence underscores the need for enhanced therapeutic strategies. Locally advanced BCC presents unique challenges, often necessitating aggressive interventions to prevent disfigurement and functional impairment. The emergence of hedgehog pathway inhibitors (HHIs) offers promising therapeutic avenues by targeting aberrant hedgehog signaling, a key driver in BCC pathogenesis. Thus, elucidating the pathogenesis of locally advanced BCC and exploring the role of HHIs are critical endeavors in effectively managing this prevalent carcinoma. Epidemiologically, BCC primarily affects individuals with fair skin and chronic sun exposure, with an increasing incidence noted among younger age groups. Risk factors include UV radiation exposure, familial history of skin cancer, immunosuppression, and genetic syndromes such as basal cell nevus syndrome and xeroderma pigmentosum. Pathogenetically, BCC arises from cells in the skin's epidermis, with hedgehog pathway activation being a primary genetic driver, involving mutations in PTCH1 and SMO. Resistance to hedgehog inhibitors may occur due to genetic changes, complicating treatment strategies. BCC is characterized by low immunogenicity, which hinders immune response and contributes to treatment challenges. Enhanced understanding of the epidemiology, risk factors, and pathogenesis of locally advanced BCC, along with the development of targeted therapeutic approaches such as hedgehog pathway inhibitors, is essential for effectively managing this prevalent carcinoma and improving patient outcomes.

Basal Cell Carcinoma: Comprehensive Review with Emphasis on Scar Tissue Manifestation and Post-Vaccination Incidence.

Basal cell carcinoma (BCC) arising within scar tissue is a rare but clinically significant phenomenon. This comprehensive review aims to provide a succinct overview of the current state of knowledge regarding the etiological factors, pathogenesis, clinical presentation, and management of BCC. This study constitutes a literature review pertaining to BCC, with a particular emphasis on BCC developing within scar tissue. It also provides a clinical case presentation of a patient who had developed BCC in a BCG post-vaccination scar and a review of analogous findings available in the existing literature. Despite the fact that an array of mechanisms play a role in injury-related BCC growth, the main mechanism remains ambiguous and yet to be elucidated. The review also includes a detailed description of the various therapeutic options available for BCC, ranging from surgical interventions to novel pharmacological treatments. By examining these intersections, the review seeks to elucidate the potential mechanisms, identify risk factors, and suggest considerations for clinical practice. The findings underscore the importance of vigilant dermatological assessment in patients with scar tissue and those recently vaccinated, aiming to improve early detection and optimize management strategies for BCC.

Dysembryogenetic Pathogenesis of Basal Cell Carcinoma: The Evidence to Date.

The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for both onset and spread. A potential correlation between the onset of BCC and a dysembryogenetic process has long been hypothesised. A selective investigation of PubMed-indexed publications supporting this theory retrieved 64 selected articles published between 1901 and 2024. From our analysis of the literature review, five main research domains on the dysembryogenetic pathogenesis of BCC were identified: (1) The correlation between the topographic distribution of BCC and the macroscopic embryology, (2) the correlation between BCC and the microscopic embryology, (3) the genetic BCC, (4) the correlation between BCC and the hair follicle and (5) the correlation between BCC and the molecular embryology with a specific focus on the Hedgehog signalling pathway. A large amount of data from microscopic and molecular research consistently supports the hypothesis of a dysembryogenetic pathogenesis of BCC. Such evidence is promoting advances in the clinical management of this disease, with innovative targeted molecular therapies on an immune modulating basis being developed.

Investigation of Genetic Association Between a High Activity Variant of Cathepsin G and Risk for Basal Cell Carcinoma.

Cathepsin G (CTSG) has been identified as an inhibitor of breast, bladder, and colorectal cancers. The G allele of the N125S (A/G, rs45567233) functional polymorphism of the CTSG gene confers increased serum CTSG activity and has been associated with cardiovascular and neurovascular diseases. This study examined the possible correlation between the pathogenesis of basal cell carcinoma (BCC) and the functional polymorphism CTSG N125S. A total of 197 DNA samples were examined, comprising 98 BCC patients and 99 control samples of Greek origin. The CTSG N125S polymorphism was molecularly genotyped using PCR amplification, followed by enzyme digestion, and agarose gel electrophoresis of the amplified DNA fragments. There was no statistically significant difference in the genotypic and allelic frequencies between the patient and the control groups. There is no association between the CTSG N125S polymorphism and pathogenesis of BCC.

Chinese guildeline on diagnosis and treatment of basal cell carcinoma (2023 edition)

Basal cell carcinoma (BCC) is the most common skin malignancy, with a higher prevalence in Caucasians than in East Asians. Although there is a lack of epidemiological data in China, it is generally believed that the incidence of BCC in China is increasing due to the aging population. A variety of risk factors are related to the occurrence of BCC, among which ultraviolet rays and gene mutations play a major role, especially the abnormal activation of Hedgehog (Hh) signaling pathway, which is considered to be the most important pathogenesis of BCC. The clinical manifestations of BCC are highly specific, and most experienced doctors can make a preliminary diagnosis by clinical manifestations. Dermoscopy and other imaging methods can greatly improve the accuracy of diagnosis, but there are still some atypical or rare types of BCC that need further confirmation through histopathological examination. This guideline is initiated by the National Clinical Research Center for Skin and Immune Diseases (based on Peking University First Hospital). It has invited a panel of experts consisting of 24 senior dermatologists specializing in dermatologic surgery from the Dermatologic Surgery Group of the Chinese Medical Doctor Association of Dermatology, the Dermatologic Surgery Group of the Dermatology & Venereology Committee, Chinese Association of Integration Medicine, and the Dermatologic Surgery and Cosmetic Branch of Clina Leprosy Association. In addition, experts from the Burn and Plastic Surgery (Maxillofacial), Ophthalmology, Otolaryngology, Head and Neck Surgery, Radiation Therapy, and Pathology were also invited to participate. This panel forms the "Chinese Guideline for the Diagnosis and Treatment of Basal Cell Carcinoma" expert group. Based on the latest domestic and international research findings, the guideline was developed through four rounds of discussions by the expert group and revised to provide valuable references for clinical healthcare providers in the diagnosis and treatment of BCC.

Loss of ARHGAP40 expression in basal cell carcinoma via CpG island hypermethylation.

Basal cell carcinoma (BCC) is the most common malignant tumour arising from the basal cells of the epidermis or follicular structures. The aetiology of BCC is a multifactorial combination of genotype, phenotype and environmental factors. The pathogenesis of BCC remains unclear, with diverse and complex signalling pathways involved. ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). Rho GTPases play a crucial role in the formation and progression of numerous cancers. The expression levels and roles of ARHGAP40 in BCC have not been explored. Here, ARHGAP40 expression was detected in a set of formalin-fixed, paraffin-embedded (FFPE) samples of basal cell carcinoma, paracancerous normal skin and benign skin lesions. The epigenetic mechanism that downregulates ARHGAP40 in basal cell carcinoma was investigated. We found that ARHGAP40 is expressed in normal basal cells and most benign skin lesions but lost in most basal cell carcinomas. We detected CpG island hypermethylation at the promoter-associated region of ARHGAP40. Our data suggest that ARHGAP40 is downregulated in BCC due to hypermethylation. ARHGAP40 protein is a potential novel biomarker for distinguishing trichoblastoma from BCC. This report is preliminary, and extensive research into the role of ARHGAP40 in BCC carcinogenesis and its potential as a treatment target is required in the future.

Methylation status, mRNA and protein expression of the SMAD4 gene in patients with non-melanocytic skin cancers.

SMAD4 is a potent tumor suppressor. SMAD4 loss increases genomic instability and plays a critical role in the DNA damage response that leads to skin cancer development. We aimed to investigate SMAD4 methylation effects on mRNA and protein expression of SMAD4 in cancer and healthy tissues from patients with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and basosquamous skin cancer (BSC). The study included 17 BCC, 24 cSCC and nine BSC patients. DNA and RNA were isolated from cancerous and healthy tissues following punch biopsy. Methylation-specific polymerase chain reaction (PCR) and real-time quantitative PCR methods were used to examine SMAD4 promoter methylation and SMAD4 mRNA levels, respectively. The percentage and intensity of staining of the SMAD4 protein were determined by immunohistochemistry. The percentage of SMAD4 methylation was increased in the patients with BCC (p = 0.007), cSCC (p = 0.004), and BSC (p = 0.018) compared to the healthy tissue. SMAD4 mRNA expression was decreased in the patients with BCC (p˂0.001), cSCC (p˂0.001), and BSC (p = 0.008). The staining characteristic of SMAD4 protein was negative in the cancer tissues of the patients with cSCC (p = 0.00). Lower SMAD4 mRNA levels were observed in the poorly differentiated cSCC patients (p = 0.001). The staining characteristics of the SMAD4 protein were related to age and chronic sun exposure. Hypermethylation of SMAD4 and reduced SMAD4 mRNA expression were found to play a role in the pathogenesis of BCC, cSCC, and BSC. A decrease in SMAD4 protein expression level was observed only in cSCC patients. This suggests that epigenetic alterations to the SMAD4 gene are associated with cSCC. The name of the trial register: SMAD4 Methylation and Expression Levels in Non-melanocytic Skin Cancers; SMAD4 Protein Positivity. The registration number: NCT04759261 ( https://clinicaltrials.gov/ct2/results?term=NCT04759261 ).

BI31 Hereditary haemochromatosis: a risk factor for nonmelanoma skin cancer?

Abstract Hereditary haemochromatosis (HH) is an autosomal recessive disease resulting in excessive levels of iron. In a recent study, in a US population of 448 patients diagnosed with HH, a positive association between HH and nonmelanoma skin cancers (NMSCs) was observed (Pan CX, Yang K, Lau CB et al. Non-melanoma skin cancer in patients with hereditary hemochromatosis: a case–control study. J Am Acad Dermatol 2023; 88:692–4). The authors also reported that, among those who required more frequent venesection, the risk of basal cell carcinoma (BCC) was particularly elevated. In terms of the possible pathomechanism, the authors noted that oxidative stress represents a key component in the pathogenesis of both HH and BCC. Ireland has the highest prevalence of HH in the world, with research suggesting approximately 1 in 83 people is predisposed. For this reason, a study was undertaken to determine if a similar association could be observed in an Irish population. A single-centre retrospective cross-sectional analysis was undertaken on a database of patients with haemochromatosis attending the venesection department of a tertiary referral centre over 25 years (1997–2022). All histologically diagnosed NMSCs within this patient group were then recorded. Ethical approval was granted by the local hospital ethics committee. There were a total 1480 patients in the database, 65% Male (n = 956). Five were excluded due to insufficient data. Thus, 1475 patients were analysed, 64% male (n = 949). The mean current age was 60 years (range: 19–100). Only 52/1475 patients (3.5%) had a histologically diagnosed NMSC, 52% male (n = 27). HH genetic mutation: C282Y homozygous (n = 29); H63D homozygous (n = 5); C282Y/H63D compound heterozygous (n = 11); and data not recorded (n = 7). Mean ferritin at HH diagnosis 575 (range: 0–8413). Forty-three patients were diagnosed with a BCC, 58% male (n = 25), with a total of 94 BCCs. Mean age was 67 years at first NMSC diagnosis. Histological classification: nodular (n = 48); superficial (n = 19); unclassified (n = 18); infiltrative (n = 5); micronodular (n = 3); and basosquamous (n = 1). Eleven patients were diagnosed with a squamous cell carcinoma (SCC), with a total of 21 SCCs. This study had limitations. It was a single-centre, retrospective study analysing only histologically confirmed NMSCs. It is acknowledged that a small proportion of NMSCs may be diagnosed clinically, specifically superficial BCCs without histological confirmation. Only records with histology available in our institution were recorded, and it is possible that NMSCs were excised in other institutions, potentially leading to an under-representation of NMSC incidence. The proportion of patients diagnosed with NMSCs in this cohort was relatively low, in contrast to the findings reported by Pan et al. This study indicates that HH is unlikely to represent an independent risk factor.

Narrative review: mechanism of ultraviolet radiation-induced basal cell carcinoma

Background and Objective: Basal cell carcinoma (BCC) is the most widespread malignant skin cancer and also the most common cancer in adults. Although its mortality rate is low, its incidence is increasing, especially in Caucasians. Among many risk factors, ultraviolet radiation (UVR) is the essential factor in forming BCC. However, the molecular mechanisms leading to transformation are not fully understood. This review provides a comprehensive description of the interaction of UVR and genetic features in the pathogenesis of BCC, and specifically, current advances in molecular therapy based on these mechanisms are introduced.

Immunohistochemical Expression of Chemokine Receptor CXCR3 and its Ligand CXCL 11 in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common type of skin cancer worldwide. The pathogenesis of BCC involves interplay between various environmental and genetic factors. It is believed that chemokines play a significant role in the modulation of cancer growth by generating autocrine and paracrine signaling effects. The present study was conducted to elucidate the expression of chemokine, CXCL11, and its receptor CXCR3, and their interaction with tumor cells and peri-tumoral stroma in various subtypes of BCC. The aim of this study was to evaluate the immunohistochemical expression of chemokine CXCL11 and its receptor CXCR3 in various subtypes of BCC. The study included 40 cases of histopathologically confirmed BCC. Clinical and histopathological features of various tumor subtypes were noted. Immunohistochemistry was performed using antibodies against CXCL11 and CXCR3, and these were assigned scores 0, 1, and 2 on the basis of immunohistochemical expression. The median age of study participants was 65.0 ± 12.2 years with a male-to-female ratio of 1.5:1. The most common site was face, followed by neck, scalp, and back. The tumor subtypes included in the study were nodular (n = 20), pigmented (n = 8), infiltrating (n = 5), superficial (n = 4), and adenoid (n = 3). On immunohistochemistry, CXCR3 expression was seen in 34 (85%) cases with stromal inflammatory cells immunopositivity in 29 (72.5%) cases and tumor cells immunopositivity in 5 (12.5%) cases. CXCL11 expression was seen in 36 (90%) cases with weak expression in stroma and tumor in 18 cases and strong expression in the rest 18 cases. In individual subtypes, higher immunopositivity for CXCR3 and CXCL11 in tumor cells and peri-tumoral stroma was seen for nodular, infiltrating, and pigmented subtypes, compared to adenoid and superficial subtypes. Our study shows the enhanced expression of chemokine CXCL11 and its receptor CXCR3 in tumor cells and peri-tumoral stroma of BCC. This expression is greater in tumor cells of aggressive subtypes, i.e. nodular, infiltrating, and pigmented types. This suggests that receptor ligand pathway involving CXCR3 and CXCL11 plays a key role in pathogenesis of BCC, and blocking this pathway may result in inhibition of tumor growth. Thus, these chemokines may serve as future potential targets in developing novel therapeutic regimens against BCC.

The role of TGF-β and antimicrobial peptides in basal cell carcinoma: a systematic review.

Basal cell carcinoma (BCC) is the most common skin cancer in humans, occurring in more than 50% of Caucasians during their lifetime, with a frequency rate that is continually increasing. We present a systematic review summarizing the role of transforming growth factor β (TGF-β), cathelicidin, and human β-defensins (HBDs) in the pathogenesis of BCC. The major online databases including PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched to extract studies regarding the levels of TGF-β, HBD, and cathelicidin in BCC. A total of 14 studies met the inclusion criteria and were included in this systematic review. There were 6 studies that included initially established levels of TGF-β in BCCs. A total of 87 BCCs were analysed, and a common result was that the TGF-β levels increase in the BCCs compared to the control groups. Analogously, 2 studies contained numerical data on HBD levels but with a different in methodology. The level of cathelicidin was established in 108 BCCs and was significantly higher in the BCC group than in the control group. The presented review shows evidence that proteins like TGF-β, HBD, and cathelicidin play a role in developing BCC. Protein levels or their expression are elevated in patients with BCC. Furthermore, a critical review of the literature was presented and discussed, highlighting its shortcomings.

The Immune Microenvironment in Basal Cell Carcinoma.

The immune system plays a key role in the suppression and progression of basal cell carcinoma (BCC). The primary aetiological factor for BCC development is exposure to ultraviolet radiation (UVR) which, particularly in lighter Fitzpatrick skin types, leads to the accumulation of DNA damage. UVR has roles in the generation of an immunosuppressive environment, facilitating cancer progression. Rates of BCC are elevated in immunosuppressed patients, and BCC may undergo spontaneous immune-mediated regression. Histologic and immunohistochemical profiling of BCCs consistently demonstrates the presence of an immune infiltrate and associated immune proteins. Early studies of immune checkpoint inhibitors reveal promising results in BCC. Therefore, the host immune system and tumor responses to it are important in BCC pathogenesis. Understanding these interactions will be beneficial for disease prognostication and therapeutic decisions.

Expression of Hedgehog Signaling Pathway Proteins in Basal Cell Carcinoma: Clinicopathologic Study.

Basal cell carcinoma (BCC) is the most common type of cancer with a growing incidence rate over recent decades. The increasing economic burden and incidence of BCC have generated major interest in developing targeted therapies for this disease. The critical role of the Hedgehog (Hh) pathway in the pathogenesis of BCC has become evidently demonstrated. The purpose of this study was to observe the expression of PTCH1 and Gli1 in BCC and further evaluate their relationship with clinicopathological features. This retrospective study included 84 patients with BCC. Information of 84 patients with pathologically diagnosed BCC (including location, sex, tumor size, pathological type, and depth of invasion) were collected, and tissue paraffin blocks were collected for immunohistochemical staining. Western blot analysis for PTCH1 and Gli1 were also performed. The staining intensity and percentage of stained cells were expressed as a histochemical score (HSCORE). PTCH1 and Gli1 were overexpressed in BCC compared with adjacent normal epidermis. Our study found that the expression of PTCH1 and Gli1 in BCC in exposed sites was significantly higher than in non-exposed sites. Moreover, no significant difference was observed in sex, Breslow thickness, tumor size or pathological type (P>0.05). PTCH1 and Gli1 were overexpressed in BCC. Higher PTCH1 and Gli1 expression were in exposed sites lesions. Our study suggests that UV radiation may be associated with aberrant activation of the Hh-PTCH1-Gli1 intercellular signaling pathway in BCC. The molecular mechanism of UV-related PTCH1 and Gli1 differential expression deserves more rigorous research in the future.

Association Between a High Gene Expression Variant of Chymase and Increased Risk for Basal Cell Carcinoma.

Previous studies have associated certain variations in genes encoding factors of renin-angiotensin system (RAS), indirectly leading to higher angiotensin II (AngII) levels, with greater risk for basal cell carcinoma (BCC) development. Chymase (CMA1) is the main regulator of the RAS-independent AngII generation pathway and numerous studies have shown its oncogenic potential in several cancer types including BCC. In this study, we investigated the possible association between BCC pathogenesis and the functional DNA polymorphism A1903G (rs1800875) that affects expression of the CMA1 gene. We genotyped 199 DNA samples, isolated from 100 BCC patients and 99 age, sex, and ethnicity-matched healthy controls for the CMA1 A1903G polymorphism. Genotyping was performed with PCR amplification, followed by MboI enzyme digestion and agarose gel electrophoresis of the resulted DNA fragments. The variant G allele that possibly increases CMA1 gene expression was not detected at a significantly different frequency between the groups of BCC patients and healthy controls. However, the AG heterozygous genotype was significantly increased in BCC patients compared with controls (p<0.001). The high expression CMA1 G allele carriers have an increased risk for BCC and elevated levels of chymase in the skin may have a carcinogenic effect.

The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas.

Simple SummaryIn addition to mutations, ectopically-expressed genes are emerging as important contributors to cancer development. Efforts to characterize the expression patterns in cancers of gamete-restricted cancer-testis antigens and developmentally-restricted genes are underway, revealing these genes to be putative biomarkers and therapeutic targets for various malignancies. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are two highly-prevalent non-melanoma skin cancers that result in considerable burden on patients and our health system. To optimize disease prognostication and treatment, it is necessary to further classify the molecular complexity of these malignancies. This review describes the expression patterns and functions of cancer-testis antigens and developmentally-restricted genes in BCC and cSCC tumors. A large number of cancer-testis antigens and developmental genes exhibit substantial expression levels in BCC and cSCC. These genes have been shown to contribute to several aspects of cancer biology, including tumorigenesis, differentiation, invasion and responses to anti-cancer therapy. Keratinocyte carcinomas are among the most prevalent malignancies worldwide. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the two cancers recognized as keratinocyte carcinomas. The standard of care for treating these cancers includes surgery and ablative therapies. However, in recent years, targeted therapies (e.g., cetuximab for cSCC and vismodegib/sonidegib for BCC) have been used to treat advanced disease as well as immunotherapy (e.g., cemiplimab). These treatments are expensive and have significant toxicities with objective response rates approaching ~50–65%. Hence, there is a need to dissect the molecular pathogenesis of these cancers to identify novel biomarkers and therapeutic targets to improve disease management. Several cancer-testis antigens (CTA) and developmental genes (including embryonic stem cell factors and fetal genes) are ectopically expressed in BCC and cSCC. When ectopically expressed in malignant tissues, functions of these genes may be recaptured to promote tumorigenesis. CTAs and developmental genes are emerging as important players in the pathogenesis of BCC and cSCC, positioning themselves as attractive candidate biomarkers and therapeutic targets requiring rigorous testing. Herein, we review the current research and offer perspectives on the contributions of CTAs and developmental genes to the pathogenesis of keratinocyte carcinomas.

Basal cell carcinoma: An updated review of pathogenesis and treatment options.

Basal cell carcinoma (BCC) remains the most common malignancy worldwide. BCC pathogenesis is a result of the interplay between one's environment, genetics, and phenotypic factors. BCC has a low mortality but given its increasing incidence and potential to cause local destruction thus resulting in significant morbidity, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. This article provides a comprehensive review of the pathogenesis of BCC as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to BCC's recommended treatment modalities.

Basal cell carcinoma-clinico-pathological study in Eastern India in correlation with different risk factors.

To study the histological variants and mimickers of basal cell carcinoma (BCC) alongwith different risk factors among a group of patients from eastern India. The specimen for the study was sent by the dermatology department for histopathology after skin biopsy. Out of 42 patients, 15 patients studied were males and the rest of the cases were females. The male to female ratio was 0.55:1. Maximum (15 cases) cases were in the age group of 50-59 years. Apart from sunlight, chronic arsenic exposure is an important risk factor of BCC. Basal cell hyperplasia and squamous cell carcinoma are the histological differential diagnosis of nodular BCC and basosquamous BCC. BCC is a disease of the older age group and with female preponderance in our study. Nodular basal cell carcinoma was the most common histologic type of basal cell carcinoma. The face was the most common site for BCC followed by the scalp. UV radiations and Arsenic do play role in the pathogenesis of BCC. CD10 helps differentiate superficial BCC from basal cell hyperplasia.

Efficacy of Acitretin Monotherapy on Basal Cell Carcinoma: A Case Report

Introduction: Basal cell carcinoma (BCC) is the most common skin cancer which mainly affects the population over 50 years of age. In addition to surgical treatment, nonsurgical treatment is also an attractive option for some patients. We herein report a case of an 82-year-old man with BCC successfully treated with acitretin. Case presentation: An 82-year-old man presented with BCC on his left nose wing more than 2 years ago. Due to his unwillingness to accept treatment that may lead to pain, discomfort, or trauma, the patient was prescribed oral acitretin 25 mg twice daily [0.8 mg/(kg·d)] and was instructed to apply 2% fusidic acid cream topically once daily for trauma protection. The lesion progressively shrank in size after 4 weeks of treatment, and was almost completely resolved after 28 weeks of follow-up. The patient reported mild adverse effects, such as mild skin fragility and cheilitis, and apparent scaling skin, which caused minor discomfort but did not affect the continuation of treatment. Discussion: The pathogenesis of BCC is still unclear, but it has been demonstrated to be linked to overactive hedgehog signaling and its crosstalk with other pathways such as phosphoinositide 3-kinase and mammalian target of rapamycin. Acitretin could obviously inhibit cell growth and proliferation and down-regulate AMP-dependent protein kinases that plays critical role in the blocking of malignant progression of several tumors including BCC. Conclusion: We provide an effective alternative for the patients with BCC who are unwilling to receive surgical therapy.

The Immunogenetics of Non-melanoma Skin Cancer.

Non-melanoma skin cancer (NMSC) is the most common malignancy seen in Caucasians and includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of NMSC is showing an increasing trend which is attributed to the increased use of sunbeds, recreational sun exposure, aging population, and partly to improved screening and reporting. Ultraviolet (UV) radiation plays the most crucial role in the pathogenesis of both BCC and SCC by inducing DNA damage and mutagenic photoproducts. Other risk factors are fair skin, old age, genetic predisposition, immunosuppression, ionizing radiation, organic chemicals, and HPV infection. The role of genomic instability, genetic mutations/aberrations, and host immunity has been fairly illustrated in several studies. This chapter aims to discuss these aspects of NMSC in detail.

Review of the Molecular Genetics of Basal Cell Carcinoma; Inherited Susceptibility, Somatic Mutations, and Targeted Therapeutics.

Simple SummaryBasal cell carcinoma is the most common human cancer worldwide. The molecular basis of BCC involves an interplay of inherited genetic susceptibility and somatic mutations, commonly induced by exposure to UV radiation. In this review, we outline the currently known germline and somatic mutations implicated in the pathogenesis of BCC with particular attention paid toward affected molecular pathways. We also discuss polymorphisms and associated phenotypic traits in addition to active areas of BCC research. We finally provide a brief overview of existing non-surgical treatments and emerging targeted therapeutics for BCC such as Hedgehog pathway inhibitors, immune modulators, and histone deacetylase inhibitors. Basal cell carcinoma (BCC) is a significant public health concern, with more than 3 million cases occurring each year in the United States, and with an increasing incidence. The molecular basis of BCC is complex, involving an interplay of inherited genetic susceptibility, including single nucleotide polymorphisms and genetic syndromes, and sporadic somatic mutations, often induced by carcinogenic exposure to UV radiation. This review outlines the currently known germline and somatic mutations implicated in the pathogenesis of BCC, including the key molecular pathways affected by these mutations, which drive oncogenesis. With advances in next generation sequencing and our understanding of the molecular genetics of BCC, established and emerging targeted therapeutics are offering new avenues for the non-surgical treatment of BCC. These agents, including Hedgehog pathway inhibitors, immune modulators, and histone deacetylase inhibitors, will also be discussed.