Basal Cell Carcinoma: A Comprehensive Review (original) (raw)
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Genome-Wide Expression Difference of MicroRNAs in Basal Cell Carcinoma
Journal of Immunology Research, 2021
Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin ( n = 15 ; control group) and tissues at tumor centers from patients with cheek BCC ( n = 15 ; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, a...
MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma
Oncogenesis, 2012
Basal cell carcinoma (BCC) of the skin represents the most common malignancy in humans. MicroRNAs (miRNAs), small regulatory RNAs with pleiotropic function, are commonly misregulated in cancer. Here we identify miR-203, a miRNA abundantly and preferentially expressed in skin, to be downregulated in BCCs. We show that activation of the Hedgehog (HH) pathway, critically involved in the pathogenesis of BCCs, as well as the EGFR/MEK/ERK/c-JUN signaling pathway suppresses miR-203. We identify c-JUN, a key effector of the HH pathway, as a novel direct target for miR-203 in vivo. Further supporting the role of miR-203 as a tumor suppressor, in vivo delivery of miR-203 mimics in a BCC mouse model results in the reduction of tumor growth. Our results identify a regulatory circuit involving miR-203 and c-JUN, which provides functional control over basal cell proliferation and differentiation. We propose that miR-203 functions as a 'bona fide' tumor suppressor in BCC, whose suppressed expression contributes to oncogenic transformation via derepression of multiple stemness-and proliferation-related genes, and its overexpression could be of therapeutic value.
Basal cell carcinoma — molecular biology and potential new therapies
Journal of Clinical Investigation, 2012
Basal cell carcinoma (BCC) of the skin, the most common malignancy in individuals of mixed European descent, is increasing in incidence due to an aging population and sun exposure habits. The realization that aberrant activation of Hedgehog signaling is a pathognomonic feature of BCC development has opened the way for exciting progress toward understanding BCC biology and translation of this knowledge to the clinic. Genetic mouse models closely mimicking human BCCs have provided answers about the tumor cell of origin, and inhibition of Hedgehog signaling is emerging as a potentially useful targeted therapy for patients with advanced or multiple BCCs that have hitherto lacked effective treatment.
Skinmed
Basal cell carcinoma (BCC) is a relatively common form of cancer with a favorable prognosis when treated early. Although most BCCs are easily treated by surgical methods, these lesions occasionally progress to an advanced state that is no longer conducive to surgery or radiation therapy. Even more rarely, the lesions spread to distant sites. Until recently, treatment for locally advanced and metastatic BCC were restricted to chemotherapy and radiation; however, the effectiveness of traditional chemotherapeutic methods in treating locally advanced or metastatic BCC is limited at best. Recent discoveries in the fields of molecular biology have found important pathways implicated in the pathogenesis of BCC. Among these are the epidermal growth factor receptor and hedgehog pathways, which are now being targeted by new biologic therapies. Despite a paucity of phase II and III trial data, preliminary evidence demonstrating the disease-stabilizing ability of biologic therapies in locally a...
Biochemical pathways and targeted therapies in basal cell carcinoma: A systematic review
Journal of Surgical Dermatology, 2016
Basal cell carcinoma (BCC) is the most common type of human malignancy. It is a slow-growing skin cancer with little ability to metastasize, but it is aggressive and can cause local tissue destruction. Descriptions of Basal Cell Nevus Syndrome (BCNS), characterized by a predisposition to the formation of BCC and other neoplasms, and identification of the genetic defect in this syndrome, has led to significant advancement in our understanding of the pathogenesis of BCC. Unregulated expression of target genes in the sonic Hedgehog (SHH) signaling pathway plays a prominent role in the pathogenesis of BCC. An understanding of the signaling components has allowed for the development of pharmacologic agents that inhibit the SHH pathway. The first inhibitor of the SHH pathway approved by the Food and Drug Administration (FDA) for the treatment of BCC is vismodegib. In this review, we will discuss the biochemical pathways involved in BCC as targets of novel pharmacologic therapies.
Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches
Biomedicines, 2020
Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhi...
Molecular alterations in basal cell carcinoma subtypes
2021
A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour. We performed in-depth analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter) in 57 BCC lesions (26 superficial and 31 nodular) from 55 patients and their corresponding blood samples. PTCH1 and TP53 mutations were found in 71.9% and 45.6% of BCCs, respectively. A high mutation rate was also detected in CSMD1 (63.2%), NOTCH1 (43.8%) and DPP10 (35.1%), and frequent non-coding mutations were identified in TERT (57.9%) and DPH3 promoter (49.1%). CSMD1 mutations significantly co-occurred with TP53 changes (p = 0.002). A significant association was observed between the superficial type of BCC and PTCH1 (p = 0.018) and NOTCH1 (p = 0.020) mutations. In addition, PTCH1 mutations were significantly associated with intermittent sun exposure (p = 0.046) and...
Basal cell carcinoma: a dermatopathological and molecular biological update
British Journal of Dermatology, 2003
The ideal classification of basal cell carcinoma (BCC) should be able to identify subtypes which correlate with clinical behaviour and treatment requirements. Unfortunately, however, such a classification has yet to be defined. In the interim, the currently most favoured classification is one based predominantly on histological growth pattern. This classification contributes to the useful concept of low-and high-risk histological subtypes of BCC. The latter are characterized by an increased probability of subclinical extension and ⁄ or incomplete excision and ⁄ or aggressive local invasive behaviour and ⁄ or local recurrence. The Royal College of Pathologists has published a minimum dataset for the histopathological reporting of BCC and this has been written to be compatible with the British Association of Dermatologists' management guidelines. Growth patterns to be reported include nodular, superficial, infiltrative ⁄ morphoeic and micronodular types, together with differentiation when of severely atypical or malignant squamous type (basosquamous carcinoma). Deep and peripheral excision margins will be reported to be either involved or clear. The latter will include a comment of a clearance of less than 1 mm for close margins and a measured distance in whole millimetres for other excisions. Clinical assessment and histology remain the 'gold standard' for evaluating BCC and cancers in general. However, in the postgenomic era emphasis is changing from the gathering and archiving of genomic data to its analysis and use in guiding clinical practice. In this context, a current goal is to define cancer phenotype in terms of molecular abnormalities and use this as a new gold standard. One way to assess whether this goal is being achieved for BCC is to determine whether our knowledge of its molecular pathology has any relevance to the minimum dataset for histological reporting. Knowledge of BCC molecular pathology has been fuelled by the recent discovery that deregulation of the Hedgehog (Hh) signalling pathway, a key player in embryonic patterning, appears to be fundamental to tumour growth. But despite accrual of a large amount of data concerning Hh pathway molecular alterations in neoplasia, little is known about the functional consequences of these changes in BCC, how they lead to tumour development, or how they relate to non-Hh pathway alterations such as TP53 mutation. Recent work suggests that the cellular localization of b-catenin gives a degree of credence to the growth pattern classification of BCC. Furthermore, it is possible that b-catenin may have a pathogenetic role in the invasive behaviour of BCC. This review draws on current evidence to discuss these issues and assess whether they are relevant to the minimum dataset.
Molecular aetiology and pathogenesis of basal cell carcinoma
British Journal of Dermatology, 2005
Recent insights into the cell biology of the epidermis and its appendages are transforming our understanding of the pathogenesis of basal cell carcinoma (BCC). The significant progress that has been made warrants a comprehensive review of the molecular and cellular pathology of BCC. The items addressed include environmental and genetic risk factors, the biology of the putative precursor cell(s), and the contribution of aberrations in processes such as apoptosis, cell proliferation, differentiation and signalling to carcinogenesis. Furthermore, established and novel treatment modalities are discussed with particular attention to future biological approaches.
Basal Cell Carcinoma Aggressiveness, Molecular Factors And Therapy: A Clinician Perspective
Basal cell carcinoma represents the most common skin and epithelial cancer. Most of the patients are cured by surgery. However, some cases display fullblown aggressiveness which has a dual connotation. The tumour may reach an impressive size being locally destructive while in rare cases, basal cell carcinomas may metastasize. If this agressivetumour is located on the face or neck, the surgeon is confronted with a clinical dilemma since total removal of the lesion with clear margins is impossible. Therefore, nonsurgical approaches need to be adopted in these cases. A better understand of the molecular pathways could theoretically lead to new improved therapeutic treatments. The current paper presents an update on the molecular factors with clinical importance for the treatment of basal cell carcinoma in parallel with presentation of an aggressive case as well as a review of the current therapeutic methods.