No approved-drug candidate for skin carcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
RCSB Protein Data Bank · entry 8AOJ · 1.12 Å · ligand 1-[(2~{S})-2-(5-methyl-3-pyridin-4-yl-1~{H}-pyrazol-4-yl)pyrrolidin-1-yl]propan-1-one (N8L). Experimental structure, not a prediction.
The 2014 review of skin cancer in the U.K. documents a steady rise in incidence of both melanoma and nonmelanoma skin cancers since the mid-twentieth century, driven by an ageing population and recreational sun exposure. Treatment costs were estimated at £106–£112 million in 2008, with a predicted rise to at least £180 million by 2020. Histopathology records from Scotland in 2012 gave provisional totals of over 20,000 skin cancers for a population of around 5 million, and extrapolation suggests at least 260,000 skin cancers are treated annually in the U.K. Registry data were found to underestimate basal cell carcinoma numbers by a factor of 2.0–2.2 compared with histopathology records. The review notes that sun exposure is the main environmental cause of both melanoma and NMSC, and that sunbed use increases risk of squamous cell carcinoma and melanoma. Evidence for the effectiveness of primary prevention campaigns is limited. Large observational studies suggesting a protective effect of high serum vitamin D have not been confirmed by randomised controlled trials, and the authors state it appears likely that low vitamin D is a result rather than a cause of ill health. A population-based screening programme in Schleswig-Holstein, Germany claimed a 50% reduction in melanoma mortality after 5 years, but other educational interventions reduced melanoma thickness without reducing cumulative mortality. The review concludes that only limited studies support population-based early detection measures and that properly controlled randomised trials are needed.
Regarding treatment, the 2014 review states that the majority of skin cancers can be controlled by existing treatments, particularly surgery, but there is a paucity of treatments for aggressive or metastatic disease. Early trials of the Hedgehog pathway inhibitor vismodegib were promising in advanced basal cell carcinoma. Selective inhibitors of mutant BRAF, such as vemurafenib, showed a survival benefit in melanoma but multiple complex resistance mechanisms became evident. Ipilimumab, a CTLA4-targeting monoclonal antibody, was noted as one immunotherapeutic agent under investigation. For squamous cell carcinoma, treatments for advanced or metastatic disease have had limited effects on overall or progression-free survival, and new systemic treatments are badly needed. The review notes that patients receiving vemurafenib often develop new well-differentiated squamous cell carcinomas bearing higher levels of activating H-Ras/K-Ras mutations than sporadic cases. The question of whether treating a field of cancerization prevents SCC development has yet to be answered in a substantial long-term randomised controlled trial.
A 2018 retrospective study from Tunisia examined 186 patients with 204 cutaneous carcinomas of the head and neck treated surgically over 12 years. Mean age was 65±13 years with male predominance. Repair of skin loss used simple suture in 42.6% of cases, flaps in 55%, directed healing in 1.9%, and skin graft in 0.5%. Recurrence occurred in 13 patients, 7 with squamous cell carcinoma and 6 with basal cell carcinoma. Predictors of recurrence were the number of carcinomas greater than one per patient (p=0.032) and invaded histological margins (p=0.001). Factors influencing aesthetic outcome were carcinoma size greater than 10mm (p=0.035) and degree of infiltration (p=0.001). The authors acknowledge the retrospective character limits the work. A 2024 review summarises that multidisciplinary therapies added to resection are often associated with improved outcomes in locally advanced or metastatic cutaneous malignancies, but provides no quantitative efficacy data. A 2023 review states that despite improved detection and treatment approaches, skin cancer continues to be a leading cause of death, and that the mechanism of skin carcinogenesis is currently poorly understood.
What remains missing is robust randomised controlled trial evidence for population-based screening, for altering sun avoidance advice or routine vitamin D supplementation, and for field cancerisation treatment to prevent squamous cell carcinoma. For advanced squamous cell carcinoma specifically, no systemic treatment has shown meaningful impact on survival. The 2018 surgical study is limited by its retrospective design and single-centre nature. No data are presented from randomised trials comparing surgical, radiation, or systemic approaches in the 2024 review, and the 2023 review offers no new clinical results. Adequate resources to manage the effects of awareness campaigns, and properly controlled trials with mortality endpoints, are still needed.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Dermatology · 2014 · 31 citations · open access
Progress in skin cancer: the U.K. experience
AbstractWhen celebrating the 125‐year anniversary of the British Journal of Dermatology (BJD), we are highlighting its long and distinguished record in publishing on skin cancer, covering many topics from skin cancer epidemiology to the basic molecular mechanisms of carcinogenesis. Skin cancer prevention and treatment are frequently addressed, and the publication and maintenance of well‐considered national and international treatment guidelines are of particular value to the hard‐pressed clinician. A number of questions remain to be answered. The incidence of skin cancer has been increasing steadily in fair‐skinned individuals since the mid‐twentieth century, particularly for nonmelanoma (keratinocyte) skin cancers (NMSCs), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as melanoma. Dermatology services in the U.K. are increasingly stressed by this rise, which is resulting from an ageing population and increasing recreational sun exposure. Use of hospital episode statistics suggested that the cost of skin cancer treatment was in the range of £106–£112 million in 2008, but a rise to at least £180 million was predicted for 2020.1 With a shortage of consultants in rural and remote areas in the U.K., dealing with this increase means we have to rethink the pattern of skin cancer services. New proposals centre around the introduction of high‐volume, consultant‐led intermediary care services being able to provide treatments for uncomplicated skin cancers, or the development of specialty doctor‐led skin cancer clinics. Many cancer registries record only the first case of NMSC but, as we know, patients often have multiple tumours, which leads to serious underestimates of total case numbers. A systematic review of 75 studies comparing incidence data with U.K. cancer registry data recognized that average incidence rates of NMSC varied geographically in England (being highest in the south west of England),2 probably reflecting regional differences in ethnicity, as well as sun exposure. The total number of BCCs in the east of England was estimated to be 2·0–2·2 times lower in registry data than in histopathology records, which gave an estimate of total BCCs in the U.K. to be 247 000, although this did not include patients treated with cryotherapy or topical therapy without pathology.3 In 2012, Scottish histopathology records gave provisional numbers of total skin cancers as > 20 000 for a population of around 5 million (Brewster, personal communication). Although this includes re‐excisions it does not include cryotherapy or topical therapy without pathology so is probably a reasonable basis for estimates. Extrapolating to the whole of the U.K. suggests that there are at least 260 000 skin cancers treated every year in the U.K. The most accurate feed to estimate the burden of disease and case numbers would appear to be from histopathology data and so a new initiative to register all NMSCs by use of a new tool for systematic recording from multidisciplinary teams is particularly helpful (http://www.rcpath.org/clinical-effectiveness/dataset-and-tissue-pathways).4 Extensive evidence from epidemiological, animal and clinical studies shows that sun exposure is the main environmental cause of both melanoma and NMSC.5 Studies also suggest that early‐life exposure is important for skin cancer and that sunbed use increases the risk of SCC and melanoma. Therefore, many skin cancer agencies have focused primary prevention programmes on sun avoidance/photoprotection (Slip Slop Slap Australia; SunSense U.K.; Sunwise U.S.A.), although evidence of their effectiveness is limited.6 However, ultraviolet (UV) B radiation is a major source of vitamin D in the skin, which has caused controversy and confusion in the mind of the public. Vitamin D is well known to be critical for bone health but recent attention has focused on the association between low vitamin D concentrations and other disorders, including cancer, cardiovascular disease, autoimmune disease, dementia and diabetes. Although large‐scale observational studies suggest that high serum concentrations of vitamin D might be protective, the results of randomized controlled trials have shown no reduction of risk; therefore, it appears likely that a low level of vitamin D is a result rather than a cause of ill health.7 Therefore, given that the doses for the development of skin cancer are higher than those for vitamin D synthesis (5–10 min face and forearm exposure), should recommendations for sun protection be changed to accommodate the need to increase vitamin D levels?8 This requires robust evidence that an increase in vitamin D status decreases the risk of cancer. What is the safest way to increase this, given the well‐established link between skin cancer risk and UV radiation? Although some have taken a pragmatic approach to recommend vitamin D supplementation,9 there is currently no robust randomized control trial evidence for altering sun avoidance advice or routine supplementation. Early detection of skin cancer has been a public health concern for over a century, with the assumption that detection of asymptomatic disease improves patient outcomes, and the World Health Organization has identified 10 fundamental principles that need to be fulfilled by a screening test.10 The critical outcome of importance for screening is a reduction in mortality. However, earlier diagnosis does not necessarily extend lifespan and can lead to overdiagnosis and overtreatment. In studies of melanoma, increases in total disease rate are being driven by changes in the proportion of early disease with almost no differences in the incidence of late‐stage disease. Skin cancer screening involves whole‐body examinations of healthy individuals for the early detection of skin cancers, which then need intervention. A population‐based screening programme (SCREEN) in Schleswig‐Holstein, Germany, trained nondermatology observers and claimed a 50% reduction in mortality after 5 years.11 Other studies using educational interventions also found a reduction in melanoma thickness but no reduction in cumulative mortality.6 12 False positives lead to anxiety, stress and scarring from unnecessary surgery. Skin cancer education campaigns, such as Euromelanoma,13 raise awareness and case numbers but the ratio of interventions to accurate diagnosis can be very high and actually reduce the speed of diagnosis for symptomatic patients when services are flooded, and adequate resources need to be available to deal with the effects of such campaigns. There may be an argument for screening patients with familial or acquired (e.g. immunosuppression)14 skin cancer risks but, taken together, only limited studies support the effectiveness of population‐based measures for the early detection of skin cancer; properly controlled randomized trials are needed. The treatment of skin cancers has been an important reason to develop national U.K. and international European guidelines for the management of skin cancers. The BJD has played a key role in the publication and updating of national U.K. guidelines, developed through the British Association of Dermatologists (BAD), for melanoma, BCC, Bowen disease and actinic keratosis.15 16 17 18 BAD guidelines for primary cutaneous SCC published in 2002,19 updated in 2009,20 have this year been joined by guidelines from the Scottish Intercollegiate Guideline Network.21 Although the majority of cases can now be controlled by existing treatments, particularly surgery, there is a paucity of treatments for aggressive or metastatic disease, and this is currently an exciting area of translational research. The genomic landscapes of common cancers have been revealed by novel sequencing techniques, with some genes (approximately 140), which are altered in a large number of tumours, being considered driver mutations involved in regulating cell fate, survival and genome maintenance.22 Mutations in oncogenes and tumour suppressor genes play an important role in skin carcinogenesis and have been identified in melanoma, BCC and, more recently, SCC. The advent of next‐generation sequencing is both facilitating and complicating this field by illustrating a very high burden of mutations in SCC (as well as BCC and melanoma), which makes the determination of driver genes more difficult.23 However, earlier studies have identified important therapeutic targets in BCC and melanoma. The activation of Hedgehog signalling by mutations in PTCH1 and SMO was shown to be sufficient for basal cell carcinogenesis.24 Small‐molecule inhibitors of the Hedgehog signalling pathway have been developed, and early trials, e.g. of vismodegib, have been promising in the treatment of aggressive or advanced disease.25 26 B‐Raf is a serine threonine kinase that activates the mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase signalling pathway. Following the discovery of B‐Raf mutations in melanoma,27 it has become clear that about 50% of melanomas harbour such mutations, predominantly BRAF V600E. Selective inhibitors of mutant BRAF, such as vemurafenib, have shown encouraging results in demonstrating a survival benefit, but multiple complex resistance mechanisms have become evident. However, melanoma has been considered to be an immunogenic tumour, and renewed interest in immunotherapy has led to new clinical trials. Ipilimumab, a fully human IgG1 monoclonal antibody that targets CTLA4 on effector and regulatory T cells leading to T‐cell hyper‐responsiveness, is one such agent. Melanoma is also thought to evade the immune system by expression of programmed death ligand (PDL)1, and, in preliminary studies, genetically engineered monoclonal antibodies to the PD–PDL1 interaction on lymphocytes are encouraging.28 Combination trials appear to be the way forward.29 The majority of SCCs can readily be treated by surgery or other available techniques, but treatments for advanced aggressive or metastatic disease have had limited effects on overall survival or progression‐free survival, and new systemic treatments are badly needed. The promise of new genomics in directing personalized tumour therapies is yet to be realized for SCC. New findings of mutations in Notch signalling pathways, Card 11 and cyclic adenosine monophosphate‐response element binding protein (CREB) binding protein have to be assessed functionally but should lead to new insights.23 30 Testing of Polo1 kinase inhibitors has shown early promise in preclinical models.31 Epidermal growth factor receptor inhibitors such as cetuximab may also have a role.32 It is well known that NMSCs arise in areas of field cancerization, with multiple actinic keratoses being a surrogate marker of SCC risk. Clonal islands of p53 expression have been known for some time in normal/sun‐exposed skin,33 and there are estimates that the skin of an individual will have many mutant clones.34 Patients receiving vemurafenib often develop new, well‐differentiated SCCs that bear a higher level of activating mutations in H‐Ras/K‐Ras than SCCs from sporadic cases, which suggests that there are also islands of Ras mutation in normal skin. This suggests that apparently normal sun‐exposed skin may be bearing many UV‐induced mutations, and understanding how these progress into visible lesions is important. It also raises the question of whether treating a field of cancerization will prevent the development of SCC, which has yet to be answered in a substantial long‐term randomized control trial of a defined population. There are lots of exciting questions to answer in basic, translational and clinical skin cancer research that will change the landscape for our patients, and the BJD will continue to bring these issues to our attention.
https://doi.org/10.1111/bjd.13258Cancers · 2024 · 6 citations · open access
The Role of Radiation, Immunotherapy, and Chemotherapy in the Management of Locally Advanced or Metastatic Cutaneous Malignancies
AbstractINTRODUCTION: Skin cancer impacts a significant proportion of the population. While surgical management is often the mainstay of treatment, advanced or metastatic cutaneous malignancies require additional local and/or systemic therapies. METHODS: A review of the literature was performed studying the use of radiation therapy, chemotherapy, and immunotherapy for locally advanced or metastatic cutaneous malignancies. RESULTS: A summary of the present literature on the management of locally advanced or metastatic cutaneous malignancies is presented across cutaneous head and neck basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The addition of multidisciplinary therapies to resection is often associated with improved outcomes. CONCLUSION: The management of cutaneous head and neck malignancies requires an approach integrating multiple specialties, to optimize outcomes and minimize toxicities.
https://doi.org/10.3390/cancers16233920Current Drug Delivery · 2023 · 3 citations
An Insight on Skin Cancer About Different Targets With Update onClinical Trials and Investigational Drugs
AbstractCancer is a diverse disease caused by transcriptional changes involving genetic and epigenetic features that influence a huge variety of genes and proteins. Skin cancer is a potentially fatal disease that affects equally men and women globally and is characterized by many molecular changes. Despite the availability of various improved approaches for detecting and treating skin cancer, it continues to be the leading cause of death throughout society. This review highlights a general overview of skin cancer, with an emphasis on epidemiology, types, risk factors, pathological and targeted facets, biomarkers and molecular markers, immunotherapy, and clinical updates of investigational drugs associated with skin cancer. The skin cancer challenges are acknowledged throughout this study, and the potential application of novel biomarkers of skin cancer formation, progression, metastasis, and prognosis is explored. Although the mechanism of skin carcinogenesis is currently poorly understood, multiple articles have shown that genetic and molecular changes are involved. Furthermore, several skin cancer risk factors are now recognized, allowing for efficient skin cancer prevention. There have been considerable improvements in the field of targeted treatment, and future research into additional targets will expand patients' therapeutic choices. In comparison to earlier articles on the same issue, this review focused on molecular and genetic factors and examined various skin cancer-related factors in depth.
https://doi.org/10.2174/1567201820666230726150642Journal of Dermatology and Skin Science · 2022 · 2 citations · open access
Commentary: Sport-specific Factors Impacting Solar Ultraviolet Exposure in Individuals Who Perform Outdoor Sport Activities
AbstractThe epidemiologic and molecular links between ultraviolet radiation (UVR) exposure and subsequent development of both melanoma and nonmelanoma skin cancers have been well elucidated. This relationship is explained by the tendency of UVR to form DNA-damaging reactive oxygen species, increase production of local growth factors, and impair cutaneous immune function in the skin.
https://doi.org/10.29245/2767-5092/2022/2.1151Current Opinion in Otolaryngology & Head & Neck Surgery · 1995 · 1 citations
The biology of skin cancer
AbstractAdvances in understanding the pathogenesis of skin cancer have occurred rapidly in the past few years. The molecular events involved in the control of normal keratinocyte growth and differentiation are being rapidly defined. In skin cancer, these normal controls are lost. Determining the molecular basis of the loss of control of keratinocyte growth in cancer will aid in the development of new and more effective treatments of this disease. Recent advances in understanding the molecular basis of nonmelanoma skin cancer are presented.
https://doi.org/10.1097/00020840-199503040-00001Tunisian Scientific and Technical Information Portal · 2018 · 0 citations · open access
Les Carcinomes cutanés de la tète et du cou. étude épidémiologique et résultats du traitement chirurgical:à propos de 186 patients
AbstractIntroduction: The skin carcinomas of the head and neck are a frequent pathology, it seen more and more in young people than usual and belonging more and more to urban areas. The clinical behaviors and scalable of these tumors are very variable depending on their histological type, their location, their size and their supported surgery. The purpose of our work is to study the epidemiological characteristics of the skin carcinomas, discuss the therapeutic indications and evaluate the results of the surgical treatment on the carcinological plan, aesthetic and functional. Patients and Methods: Our study is retrospective descriptive and analytic, concerning 186 patients pursued of a cutaneous cell carcinoma of the head and neck (204 carcinomas) operated in the service of ENT and CCF sevice of Fattouma Bourguiba Monastir hospital, over a period of 12 years between 2003 and 2014. Results: Mean age was 65±13years (25years -93years) with a predominantly male. The actinic keratosis was the preexisting lesion found most frequently. The repair of the loss of skin substance has been made by simple suture (42.6% of cases), flaps (55% of cases), directed healing (1.9% of cases) and skin graft (0.5% of cases). The recess of the ganglion areas has been carried out in 17 patients who had squamous cell carcinomas. Recurrence was observed in 13 patients, 7 with squamous cell carcinomas and 6 with basal cell carcinomas. The study of factors that may influence the outcome and analysis uni multivariate then identified as a predictor of recurrence, the number of carcinoma (>1) for each patient (p=0.032) and the limits invaded histological (p=0.001). The factors that influence the aesthetic result were the size of carcinoma >10mm (p=0.035) and the degree of infiltration (p=0.001). However, the functional results have been appreciated for periorificiels carcinomas who have presented 46.8% of cases of carcinoma, they have been deemed nonsatisfactory that 2 patients where a microstomie has been found. Conclusion: This study contributes to define a preventive and therapeutic schema of skin carcinomas, a treatment of precarcinomatous lesions, for an early care and multidisciplinary approach of invasive carcinomas. However, the retrospective character limits this work.
https://doi.org/10.60713/pist-165414British Journal of Radiology · 1982 · 0 citations
Book reviewsThe Biology of Skin Cancer (Excluding Melanomas). A Series of Workshops on the Biology of Human Cancer, Report No. 15. 1981. Ed. by LaerumO. D. and IversenO. H.. (UICC Technical Report Series Vol. 63), pp. 263 (International Union Against Cancer, Geneva), Sw.fr. 44. ISBN 92–9018–063–3
AbstractThis book consists of a series of manuscripts compiled as the result of a workshop on skin cancer. For the most part the report represents a common consensus of all the participants. However, the controversy as to the nature of chemical carcinogenesis gives rise to an appendix to Chapter 6 where two differing opinions are expressed. It is pointed out by the authors that the majority of tumours of the skin are of epidermal origin, largely squamous-cell carcinomas, and the main emphasis is on these malignancies, although information on the dermis and dermal tumours is discussed wherever relevant.
https://doi.org/10.1259/0007-1285-55-659-852-aHolland‐Frei Cancer Medicine · 2022 · 0 citations
Other Skin Cancers
AbstractOverview Nonmelanoma skin cancer (NMSC) includes squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), and other premalignant and malignant tumor types. The incidence of NMSC has increased significantly in recent years. These cancers are diverse in their clinical presentation, biology, and capacity to metastasize. Our understanding of the molecular biology of NMSC has grown considerably in recent years, leading to the development of new treatment options. In addition to malignant NMSC, this article will discuss several benign skin tumors that arise due to underlying internal malignancies.
https://doi.org/10.1002/9781119000822.hfcm111.pub2Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
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