Structures already discussed alongside skin cancer in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
RCSB Protein Data Bank · entry 2A3B · 1.9 Å · ligand Caffeine (CFF). Experimental structure, not a prediction.
A 2021 review on repurposing drugs for skin cancer states that current therapies for melanoma and non-melanoma skin cancers still have disadvantages including little cell specificity, recurrent relapses, high toxicity, and increased costs. The same review notes that developing a new medication can take 10–15 years and is expensive, making drug repurposing an attractive alternative. No specific repurposed drug candidates or their outcomes are named in that abstract.
A 2023 review acknowledges that the mechanism of skin carcinogenesis is still poorly understood, though genetic and molecular changes are known to be involved. It mentions that targeted treatment has seen considerable improvements and that future research into additional targets could expand therapeutic options. The review does not report any numerical results from clinical trials.
A 2017 review describes fundamental gaps remaining in the biomedical puzzle of curing cancer and discusses cell signalling pathways that could be potential targets for skin cancer treatment. It does not provide any patient data.
A 2009 report on a fly-in/fly-out skin cancer clinic in remote Australia found that among 316 people seen (29% of the non-Indigenous population), the rate of skin cancer detection was 15 per 1000 adults per year. For males over 50, there was a statistically significant four-fold rise in melanoma detection, from 0.2 per 1000 people per year before the clinic to 2 per 1000 per year after. The authors note that the small population and low statistical power prevented certainty that clinical outcomes were enhanced.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Oncology · 2013 · 46 citations · open access
Mechanisms of Caffeine-Induced Inhibition of UVB Carcinogenesis
AbstractSunlight-induced non-melanoma skin cancer is the most prevalent cancer in the United States with more than two million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on non-melanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect. Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345) and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine) inhibits UVB-induced carcinogenesis support the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine's inhibitory effect on UVB-induced carcinogenesis.
https://doi.org/10.3389/fonc.2013.00144Experimental Dermatology · 2017 · 10 citations · open access
Overcoming cell death resistance in skin cancer therapy: Novel translational perspectives
AbstractIn the last decade, significant progress has been made in understanding skin cancer cell death resistance mechanisms, and a number of new treatment strategies have been developed. Systematic approach genomic studies of various cancer types have opened new possibilities for the development of anticancer therapies. However, there are still fundamental gaps in the challenging biomedical puzzle, which will form a complete picture for curing cancer. Thus, herein, we describe some of the current cancer treatment strategies and discuss additional cell signalling pathways that could be potential targets for skin cancer treatment.
https://doi.org/10.1111/exd.13309Rural and Remote Health · 2009 · 7 citations · open access
The Royal Flying Doctor Service primary care skin cancer clinic: a pilot program for remote Australia
AbstractINTRODUCTION: The geography and logistics of living in remote Australia provide unique challenges in providing dedicated primary healthcare services to tackle the rising incidence of skin cancer. The aim of this study was to ascertain whether the Royal Flying Doctor Service (RFDS) skin cancer clinic could improve skin cancer health outcomes for the target population while providing care at a level consistent with that documented for metropolitan skin cancer clinics. METHODS: This retrospective longitudinal report compared historical controls with a dedicated fly-in/fly-out primary care skin cancer outreach clinic provided by the RFDS. The clinic was run concurrently with the regular primary care medical service; the entire focus of this additional service was on skin cancer diagnosis and management. This model was used to minimise the additional costs of providing the service. RESULTS: During the study period a total of 316 people were seen at this skin cancer clinic (29% of the total non-Indigenous population) with 39% of those aged over 50 years seen. There was an average of 1.1 consultations per person (343 consultations in total), with a procedure performed in approximately one-third of consultations. The demographic most likely to have a lesion removed were over 50 year-old males (p<0.0001). The rate of skin cancer detection was 15/1000 adults/year. The number of lesions removed per year increased from 37 to 42 after the intervention, with no statistically significant change in the percentage of excised lesions that were malignant (44%). For over 50 year-old males there was a statistically significant increase in the proportion of excised lesions that were melanomas (chi2 = 6.015; p = 0.013). This corresponded to a four-fold rise in melanoma detection from 0.2/1000 people/year pre-intervention to 2/1000 people/year post-intervention. A comparison of the skin clinic's effectiveness with documented results from other Australian non-specialist skin cancer services demonstrated a low number needed to treat for melanoma which is consistent with high diagnostic accuracy. This is also supported by a relatively high consultation to biopsy ratio. The biopsy treatment ratio and percentage of lesions that were malignant were similar to those seen in other Australian settings. CONCLUSION: The RFDS skin cancer clinic outcomes were not dissimilar to those seen in metropolitan skin cancer clinics. The small population and consequently low statistical power mitigated against certainty in concluding that clinical outcomes were enhanced. Further studies would assist in the future development of models for skin cancer clinics in remote areas.
https://doi.org/10.22605/rrh1048Current 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 Skin Cancer · 2013 · 3 citations · open access
Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis
AbstractThe multistep model of mouse skin carcinogenesis has facilitated identification of irreversible genetic events of initiation and progression, and epigenetic events of tumor promotion. Mouse skin tumor initiation can be accomplished by a single exposure to a sufficiently small dose of a carcinogen, and this step is rapid and irreversible. However, promotion of skin tumor formation requires a repeated and prolonged exposure to a promoter, and that tumor promotion is reversible. Investigations focused on the mechanisms of mouse carcinogenesis have resulted in the identifications of potential molecular targets of cancer induction and progression useful in planning strategies for human cancer prevention trials. This special issue contains eight papers that focus on mouse models used to study individual proteins expressed in the mouse skin and the role they play in differentiation, tissue homeostasis, skin carcinogenesis, and chemoprevention of skin cancer.
In the paper entitled “Ap1 transcription factors in epidermal differentiation and skin cancer,” R. Eckert et al. highlight the role of AP1, a transcription factor composed of c-jun and c-fos, that serves as a central node in epidermal keratinocyte survival and differentiation. The authors discuss how AP1 deregulation leads to key steps in driving the development of cancer and how these functions in cancer may be different in epidermal development. Finally, they summarize the various mouse models that have helped elucidate the role of this very interesting molecule.
In the paper entitled “The role of TGFβ signaling in squamous cell cancer: lessons from mouse models,” A. Glick summarizes the current literature on the role of TGFβ1 in normal tissues and in carcinogenesis. TGFβ1 is a member of a large growth factor family including activins/inhibins and bone morphogenic proteins (BMPs) that have potent growth regulatory and immunomodulatory functions in normal skin homeostasis, regulation of epidermal stem cells, extracellular matrix production, angiogenesis, and inflammation. The author presents a thorough comparison between the role of TGFβ1 in signaling in human HNSCC and cutaneous SCC and the various mouse models that have been developed to elucidate the role this molecule plays in oncogenesis.
In the paper entitled “Multiple roles for VEGF in non-melanoma skin cancer: angiogenesis and beyond,” K. Johnson and T. Wilgus overview how vascular endothelial growth factor (VEGF), a potent proangiogenic factor in mouse and human skin tumors, plays a role in the development of non-melanoma skin cancers. The authors have detailed the use of both transgenic and knockout mice that have provided key clues, primarily alteration of proliferation, survival, and stemness, that have helped elucidate the function of VEGF in carcinogenesis.
In the paper entitled “Protein kinase Ce, which is linked to ultraviolet radiation-induced development of squamous cell carcinomas, stimulates rapid turnover of adult hair follicle stem cells,” A. Singh et al. report that protein kinase C epsilon (PKCe), a member of the protein kinase C superfamily, plays a critical step in the development of cutaneous SCC induced by repeated exposures to ultraviolet radiation (UV). The authors focus their investigation on how PKCe, using transgenic mice, may modulate the hair follicle stem cell (HSC). The authors report that overexpression of PKCe in the skin, driven by the K14 promoter, leads to a 7-fold increase in the proliferation of the HSC, indicating a rapid turnover of these cells.
In the paper entitled “Patched knockout mouse models of basal cell carcinoma,” the authors discuss the link Patched (PTCH), the receptor for the hedgehog ligand, in the development of Basal cell carcinoma (BCC), the most common form of human skin cancer. In this comprehensive review, the authors compare conventional and conditional PTCH knockout mouse models to investigate BCC as well as for potential use in preclinical research.
In the paper entitled “Delineating molecular mechanisms of squamous tissue homeostasis and neoplasia: focus on p63,” K. King et al. focus on summarizing mouse models that have highlighted the importance of p63, a transcription factor that plays an essential role in the development and maintenance of normal stratified squamous epithelium. The authors present that p63 has multiple splice variants and p63 plays a critical role in normal skin biology and neoplastic development.
In the paper entitled “Role of Stat3 in skin carcinogenesis: insights gained from relevant mouse models,” E. Macias et al. review the role of signal transducer and activator of transcription 3 (Stat3) in skin biology. The authors detail the various transgenic, knockout, and conditional knockout mice that have led to the understanding of STAT3 in normal skin homeostasis, migration, wound healing, and hair follicle growth and maintenance as well as skin carcinogenesis.
In the paper entitled “Topical curcumin-based cream is equivalent to dietary curcumin in a skin cancer model,” the authors present the first study that compares the use of topical curcumin versus the use of oral curcumin as a chemopreventive strategy for the development of SCC of the skin.
This collection of papers provides an overview of mouse models investigating several intensely studied molecules involved in skin carcinogenesis. We hope the molecular mechanisms revealed in this special issue will enlighten readers and provide them with motivation to continue their research endeavors.
Deric L. Wheeler
Ajit K. Verma
Mitchell F. Denning
https://doi.org/10.1155/2013/971495Greater South Information System · 2021 · 0 citations · open access
Repurposing of Drug Candidates for Treatment of Skin Cancer
AbstractSkin cancers are highly prevalent malignancies that affect millions of people worldwide. These include melanomas and nonmelanoma skin cancers. Melanomas are among the most dangerous cancers, while nonmelanoma skin cancers generally exhibit a more benign clinical pattern; however, they may sometimes be aggressive and metastatic. Melanomas typically appear in body regions exposed to the sun, although they may also appear in areas that do not usually get sun exposure. Thus, their development is multifactorial, comprising endogenous and exogenous risk factors. The management of skin cancer depends on the type; it is usually based on surgery, chemotherapy, immunotherapy, and targeted therapy. In this respect, oncological treatments have demonstrated some progress in the last years; however, current therapies still present various disadvantages such as little cell specificity, recurrent relapses, high toxicity, and increased costs. Furthermore, the pursuit of novel medications is expensive, and the authorization for their clinical utilization may take 10–15 years. Thus, repositioning of drugs previously approved and utilized for other diseases has emerged as an excellent alternative. In this mini-review, we aimed to provide an updated overview of drugs' repurposing to treat skin cancer and discuss future perspectives.
https://doi.org/10.60692/h9cez-jbq34Greater South Information System · 2021 · 0 citations · open access
Repurposing of Drug Candidates for Treatment of Skin Cancer
AbstractSkin cancers are highly prevalent malignancies that affect millions of people worldwide. These include melanomas and nonmelanoma skin cancers. Melanomas are among the most dangerous cancers, while nonmelanoma skin cancers generally exhibit a more benign clinical pattern; however, they may sometimes be aggressive and metastatic. Melanomas typically appear in body regions exposed to the sun, although they may also appear in areas that do not usually get sun exposure. Thus, their development is multifactorial, comprising endogenous and exogenous risk factors. The management of skin cancer depends on the type; it is usually based on surgery, chemotherapy, immunotherapy, and targeted therapy. In this respect, oncological treatments have demonstrated some progress in the last years; however, current therapies still present various disadvantages such as little cell specificity, recurrent relapses, high toxicity, and increased costs. Furthermore, the pursuit of novel medications is expensive, and the authorization for their clinical utilization may take 10–15 years. Thus, repositioning of drugs previously approved and utilized for other diseases has emerged as an excellent alternative. In this mini-review, we aimed to provide an updated overview of drugs' repurposing to treat skin cancer and discuss future perspectives.
https://doi.org/10.60692/9rerk-at207International Journal of Medical Science and Clinical Research Studies · 2024 · 0 citations · open access
Immunocryosurgery for Treatment of Locally Advanced BCC: A Case Report
AbstractBCC is the most common skin cancer (75%) in humans and the most common malignant tumor in the Caucasian population. The literature recognizes that 95% of BCCs are easy to treat surgically; however, when surgery is contraindicated due to patient or lesion-related conditions pharmacological and destructive therapies are reasonable alternatives. New therapeutic modalities, such as combined therapy, have been proven successful in the treatment of locally advanced and difficult-to-treat BCCs.
https://doi.org/10.47191/ijmscrs/v4-i12-13Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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