Non-Melanoma Skin Cancer – An Underestimated Global Health Threat?

Rembielak, Agata; Ajithkumar, Thankamma

doi:10.1016/j.clon.2019.08.013

Cited by 13 publications

(9 citation statements)

References 17 publications

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“…Non-melanoma skin cancer (NMSC) has been reported as one of the most common types of cancer worldwide, with an estimation of over 3 million diagnoses each year in the USA [1]. Despite including different malignancies, basal cell and squamous cell carcinomas are the most frequent types of NMSC [1][2][3]. Depending on disease risk level, surgical excision or radiotherapy are the standard treatment options.…”

Section: Introductionmentioning

confidence: 99%

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Near-Infrared Radiation-Based Mild Photohyperthermia Therapy of Non-Melanoma Skin Cancer with PEGylated Reduced Nanographene Oxide

et al. 2020

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Using a one-step thermal reduction and non-covalent chemical functionalization process, PEGylated reduced nanographene oxide (rGOn-PEG) was produced from nanographene oxide (GOn) and characterized in terms of particle size, dispersion stability, chemistry, and photothermal properties, in view of its use for photothermal therapy (PTT) of non-melanoma skin cancer. GOn infrared spectrum presented more intense bands assigned to oxygen containing functional groups than observed for rGOn-PEG. GOn C/O ratio decreased more than 50% comparing with rGOn-PEG and nitrogen was present in the latter (N at % = 20.6) due to introduction of PEG-NH2. Thermogravimetric analysis allowed estimating the amount of PEG in rGOn-PEG to be of about 56.1%. Simultaneous reduction and PEGylation increased the lateral dimensions from 287 ± 139 nm to 521 ± 397 nm, as observed by transmission electron microscopy and dynamic light scattering. rGOn-PEG exhibited ≈13-fold higher absorbance in the near-infrared radiation (NIR) region, as compared to unmodified GOn. Low power (150 mW cm−2) NIR irradiation using LEDs resulted in rGOn-PEG heating up to 47 °C, which is within the mild PTT temperature range. PEGylation strongly enhanced the dispersibility of rGOn in physiological media (phosphate buffered saline, fetal bovine serum, and cell culture medium) and also improved the biocompatibility of rGOn-PEG, in comparison to GOn (25–250 μg mL−1). After a single NIR LED irradiation treatment of 30 min, a decrease of ≈38% in A-431 cells viability was observed for rGOn-PEG (250 μg mL−1). Together, our results demonstrate the potential of irradiating rGOn-PEG using lower energy, cheaper, smaller, and safer LEDs, as alternative to high power lasers, for NIR mild hyperthermia therapy of cancer, namely non-melanoma skin cancer.

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Section: Introductionmentioning

confidence: 99%

“…Depending on disease risk level, surgical excision or radiotherapy are the standard treatment options. Severe cases of high-risk primary, recurrent, or metastatic NMSC frequently require multimodal therapy [1,[3][4][5]. However, functional and cosmetic outcomes are still variable, requiring novel treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Radiation-Based Mild Photohyperthermia Therapy of Non-Melanoma Skin Cancer with PEGylated Reduced Nanographene Oxide

et al. 2020

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“…The majority of cSCC originate from precursor lesions known as actinic keratoses (AKs) and Bowen Disease (Criscione et al, 2009; Kao, 1986). Given the ageing population, increased UV exposure, and the increase in patients on immunosuppressive regimens following procedures like organ transplantation, cSCC incidence is increasing (Rembielak & Ajithkumar 2019; Conforti et al, 2019). In the USA, an estimated 700,000 cases are diagnosed annually, with metastases from these accountable for between 3900-8800 deaths (Kauvar et al 2015; Sarin et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Phosphoproteomic analysis of the AKT signalling axis in cutaneous squamous carcinoma progression reveals novel therapeutic targets

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Harwood

O'Shaughnessy

2022

Preprint

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Cutaneous Squamous Cell Carcinoma (cSCC) represents about 20% of all non-melanoma skin cancers. Whilst generally low risk to patients, metastases are associated with a poor prognosis. cSCC incidence is increasing, owing to an ageing population, greater exposure to UV radiation, and more patients receiving immunosuppressive treatments associated with organ transplants. Therefore, there is interest in identifying new biomarkers that may be to track progression of the disease and to exploit as therapeutic vulnerabilities. We show dynamic changes in AKT expression in precursor lesions and in SCC tumour tissue, with initial loss of AKT activity followed by progressive and widespread increase in AKT activity in SCC. Phosphoproteomic analysis and kinase substrate enrichment analysis on a panel of isogenic cSCC cell lines representing different stages of the disease from premalignancy to metastasis revealed several up-regulated kinases and AKT-targets. From this analysis we chose DNA dependent protein kinase (DNA-PK), a key kinase upstream of AKT phoshorlyation, and N-Myc downstream-regulated gene 2 (NDRG2) a downstream AKT phosphorylation target, to investigate in further detail. Both proteins were up-regulated and mis-expressed in a panel of SCC tissue from different patients. We therefore explored the potential of inhibiting DNA-PK and NDRG2 as cSCC treatments. Treatment with the iron chelator Dp44mT decreased levels of phosphorylated NDRG2 and led to significant losses to viability and reduced migration in our cSCC cell lines, while DNA-PK inhibition promoted the differentiation of premalignant and early-stage SCC cell lines. Our results suggest that NDRG2 and DNA-PK may be viable targets in cSCC treatment, with effectiveness at different stages of SCC progression.

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“…Some cases, however, are locally aggressive and can exceptionally metastatize 4,5 . Furthermore, the high incidence and morbidity in the general population makes BCC a major global health threat 6 . In recent years, important progress in the knowledge of BCC genetic background has allowed development of targeted therapies 7 .…”

Section: Introductionmentioning

confidence: 99%

“…4,5 Furthermore, the high incidence and morbidity in the general population makes BCC a major global health threat. 6 In recent years, important progress in the knowledge of BCC genetic background has allowed development of targeted therapies. 7 However, histology and clinical presentation remain the gold standard to predict prognosis and decide treatment for individual cases.…”

Section: Introductionmentioning

confidence: 99%

Position paper on a simplified histopathological classification of basal cell carcinoma: results of the European Consensus Project

Fernández‐Figueras

Malvehi

Tschandl

et al. 2021

Acad Dermatol Venereol

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Background Histopathological classification of basal cell carcinoma (BCC) has important prognostic and therapeutic implications, but reproducibility of BCC subtyping among dermatopathologists is poor. Objectives To obtain a consensus paper on BCC classification and subtype definitions. Methods A panel of 12 recognized dermatopathologists (G12) from nine European countries used a modified Delphi method and evaluated 100 BCC cases uploaded to a website. The strategy involved five steps: (I) agreement on definitions for WHO 2018 BCC subtypes; (II) classification of 100 BCCs using the agreed definitions; (III) discussion on the weak points of the WHO classification and proposal of a new classification with clinical insights; (IV) re‐evaluation of the 100 BCCs using the new classification; and (V) external independent evaluation by 10 experienced dermatopathologists (G10). Results A simplified classification unifying infiltrating, sclerosing, and micronodular BCCs into a single “infiltrative BCC” subtype improved reproducibility and was practical from a clinical standpoint. Fleiss’ κ values increased for all subtypes, and the level of agreement improved from fair to moderate for the nodular and the unified infiltrative BCC groups, respectively. The agreement for basosquamous cell carcinoma remained fair, but κ values increased from 0.276 to 0.342. The results were similar for the G10 group. Delphi consensus was not achieved for the concept of trichoblastic carcinoma. In histopathological reports of BCC displaying multiple subtypes, only the most aggressive subtype should be mentioned, except superficial BCC involving margins. Conclusions The three BCC subtypes with infiltrative growth pattern, characteristically associated with higher risk of deep involvement (infiltrating, sclerosing, and micronodular), should be unified in a single group. The concise and encompassing term “infiltrative BCCs” can be used for these tumors. A binary classification of BCC into low‐risk and high‐risk subtypes on histopathological grounds alone is questionable; correlation with clinical factors is necessary to determine BCC risk and therapeutic approach.

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Non-Melanoma Skin Cancer – An Underestimated Global Health Threat?

Cited by 13 publications

References 17 publications

Near-Infrared Radiation-Based Mild Photohyperthermia Therapy of Non-Melanoma Skin Cancer with PEGylated Reduced Nanographene Oxide

Near-Infrared Radiation-Based Mild Photohyperthermia Therapy of Non-Melanoma Skin Cancer with PEGylated Reduced Nanographene Oxide

Phosphoproteomic analysis of the AKT signalling axis in cutaneous squamous carcinoma progression reveals novel therapeutic targets

Position paper on a simplified histopathological classification of basal cell carcinoma: results of the European Consensus Project

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