Immunotherapy for Non-melanoma Skin Cancer.
Ontology highlight
ABSTRACT: Purpose of review
The therapeutic landscape for non-melanoma skin cancer (NMSC) has recently expanded with the development of effective and targeted immunotherapy. Here, we provide an overview of the role of immunotherapy in the management of advanced cutaneous carcinomas.Recent findings
Several agents were recently U.S. Food and Drug Administration (FDA)-approved for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma, Merkel cell carcinoma, and basal cell carcinoma. However, recent approvals in tissue-agnostic indications may also benefit other NMSCs including cutaneous adnexal solid tumors with high tumor mutation burdens or microsatellite instability. Furthermore, while FDA-approved indications will likely continue to expand, continued studies are needed to support the role of immunotherapy in the neoadjuvant, adjuvant, and refractory settings. Immunotherapy is emerging as the standard of care for several advanced NMSCs not amenable to surgery and radiation. Ongoing evaluation of the clinical trial landscape is needed to optimize enrollment and ensure continued innovation.
SUBMITTER: Shalhout SZ
PROVIDER: S-EPMC8395379 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:(1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.
| S-EPMC5874663 | biostudies-literature
Project description:IntroductionSeveral studies have shown an increased risk of cancer after non melanoma skin cancers (NMSC) but the individual risk factors underlying this risk have not been elucidated, especially in relation to sun exposure and skin sensitivity to sunlight.PurposeThe aim of this study was to examine the individual risk factors associated with the development of subsequent cancers after non melanoma skin cancer.MethodsParticipants in the population-based New Hampshire Skin Cancer Study provided detailed risk factor data, and subsequent cancers were identified via linkage with the state cancer registry. Deaths were identified via state and national death records. A Cox proportional hazard model was used to estimate risk of subsequent malignancies in NMSC patients versus controls and to assess the potential confounding effects of multiple risk factors on this risk.ResultsAmong 3584 participants, risk of a subsequent cancer (other than NMSC) was higher after basal cell carcinoma (BCC) (adjusted HR 1.40 [95% CI 1.15, 1.71]) than squamous cell carcinoma (SCC) (adjusted HR 1.18 [95% CI 0.95, 1.46]) compared to controls (adjusted for age, sex and current cigarette smoking). After SCC, risk was higher among those diagnosed before age 60 (HR 1.96 [95% CI 1.24, 3.12]). An over 3-fold risk of melanoma after SCC (HR 3.62; 95% CI 1.85, 7.11) and BCC (HR 3.28; 95% CI 1.66, 6.51) was observed, even after further adjustment for sun exposure-related factors and family history of skin cancer. In men, prostate cancer incidence was higher after BCC compared to controls (HR 1.64; 95% CI 1.10, 2.46).ConclusionsOur population-based study indicates an increased cancer risk after NMSC that cannot be fully explained by known cancer risk factors.
| S-EPMC4061037 | biostudies-literature
Project description:Mitochondrial DNA (mtDNA) damage, predominantly encompassing point mutations, has been reported in a variety of cancers. Here we present in human skin, the first detailed study of the distribution of multiple forms of mtDNA damage in nonmelanoma skin cancer (NMSC) compared to histologically normal perilesional dermis and epidermis. We present the first entire spectrum of deletions found between different types of skin tumours and perilesional skin. In addition, we provide the first quantitative data for the incidence of the common deletion as well as the first report of specific tandem duplications in tumours from any tissue. Importantly, this work shows that there are clear differences in the distribution of deletions between the tumour and the histologically normal perilesional skin. Furthermore, DNA sequencing of four mutation 'hotspot' regions of the mitochondrial genome identified a previously unreported somatic heteroplasmic mutation in an SCC patient. In addition, 81 unreported and reported homoplasmic single base changes were identified in the other NMSC patients. Unlike the distribution of deletions and the heteroplasmic mutation, these homoplasmic mutations were present in both tumour and perilesional skin, which suggests that for some genetic studies the traditional use of histologically normal perilesional skin from NMSC patients may be limited. Currently, it is unclear whether mtDNA damage has a direct link to skin cancer or it may simply reflect an underlying nuclear DNA instability.
| S-EPMC2376793 | biostudies-other
Project description:Densely labelled segmentation data for digital pathology images is costly to produce but is invaluable to training effective machine learning models. We make available 290 hand-annotated histopathology tissue sections of the 3 most common skin cancers; basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC). These non-melanoma skin cancers constitute over 90% of all skin cancer diagnoses and hence this dataset gives an opportunity to the scientific community to benchmark analytic methodologies on a significant portion of the dermatopathology workflow. The data represents typical cases of the three cancer types (not requiring a differential diagnosis) across shave, punch and excision biopsy contexts. Each image is accompanied with a segmentation mask which characterizes the section into 12 tissue types, specifically: keratin, epidermis, papillary dermis, reticular dermis, hypodermis, inflammation, glands, hair follicles and background, as well as BCC, SCC and IEC. Included also are cancer margin measurements to work towards automated assessment of surgical margin clearance and tumour invasion. This leaves open many opportunities for researchers to utilize or extend the dataset, building upon recent work on image analysis problems in skin cancer (Thomas et al., 2021).
| S-EPMC8627989 | biostudies-literature
Project description:Background: Mohs micrographic surgery (MMS) is the gold standard treatment for high-risk facial non-melanoma skin cancer. However, patients' access to MMS is limited by cost. The muffin technique micrographic surgery (MTMS) is an alternative micrographic technique wherein the entire excised margin is evaluated post-operatively by a pathologist using paraffin-embedded material. Herein, we describe the implementation and the preliminary results of MTMS in an academic dermatology center. Objective: To describe the MTMS and outline its efficacy and safety in a real-world clinical academic setting. Methods: A retrospective chart review was conducted of all patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) who underwent MTMS at the University of Alberta Dermatology Center from June 2016 until July 2019. Results: A total of 69 patients were included (64 BCCs and 5 SCCs). 68.1% of surgeries had clear margins following the first incision, 100% after second round re-excisions. There were no observed cases of tumor recurrence after a median 40 months of follow-up. There were no major adverse events or complications. Conclusions: MTMS is a superior alternative to simple excision of skin cancer by providing full margin control and residual tumor mapping.
| S-EPMC7859636 | biostudies-literature
Project description:A milieu of cytokines and signaling molecules are involved in the induction of UV-induced immune suppression and thus the etiology of non-melanoma skin cancer (NMSC). Targeting the UV-induced immunosuppression pathway, and using a large population based study of NMSC, we have investigated the risk associated with functional variants in 10 genes (IL10, IL4, IL4R, TNF, TNFR2, HTR2A, HRH2, IL12B, PTGS2, and HAL). The most prominent single genetic effect was observed for IL10. There was increasing risk for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with increasing number of variant IL10 haplotypes (BCC: p(trend)?=?0.0048; SCC: p(trend)?=?0.031). Having two IL10 GC haplotypes was associated with increased odds ratios of BCC and SCC (OR(BCC)?=?1.5, 95% CI 1.1-1.9; OR(SCC)?=?1.4, 95% CI 1.0-1.9), and these associations were largely confined to women (OR(BCC)?=?2.2, 95% CI 1.4-3.4; SCC: OR(SCC)?=?1.8, 95% CI 1.1-3.0). To examine how combinations of these variants contribute to risk of BCC and SCC, we used multifactor dimensionality reduction (MDR) and classification and regression trees (CART). Results from both of these methods found that in men, a combination of skin type, burns, IL10, IL4R, and possibly TNFR2 were important in both BCC and SCC. In women, skin type, burns, and IL10 were the most critical risk factors in SCC, with risk of BCC involving these same factors plus genetic variants in HTR2A, IL12B and IL4R. These data suggest differential genetic susceptibility to UV-induced immune suppression and skin cancer risk by gender.
| S-EPMC3132750 | biostudies-literature
Project description:BackgroundSkin cancer is one of the common malignancies. There is sufficient evidence that sunlight (ultraviolet radiation) contributes to the development of skin cancer, but there is also evidence that relates adequate serum levels of vitamin D produced on the skin by the action of ultraviolet radiation with the decreased risk of various types of cancers, including skin cancer. The aim of this study was to investigate the association of vitamin D serum levels among patients with non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) and controls.MethodsA prospective observational case-control study was conducted in a sample of 84 subjects in Extremadura (Spain). Forty-one patients with histologically diagnosed basal cell carcinomas and squamous cell carcinomas and 43 healthy controls were randomly chosen to assess whether vitamin D (25(OH)D3) serum level, age and sex were related to non-melanoma skin cancer and to determine the possible risk of this type of skin cancer for these variables.ResultsWhen analysing serum vitamin D levels, we ensured that all our subjects, both cases and controls, had normal or low serum vitamin D levels, even though the samples were taken during months with the highest solar irradiance in our region. It is striking in our results that there was a higher percentage of subjects with deficits of vitamin D who did not have skin cancer (66%) than patients with deficits with these types of skin cancers (34%). When adjusting the model for age and sex, vitamin D values above 18 ng/ml increased the risk of suffering from non-melanoma skin cancer by nearly 7-fold (aOR: 6.94, 95% CI [1.55-31.11], p = 0.01).ConclusionsDespite the controversial data obtained in the literature, our results suggest that lower levels of vitamin D may be related to a reduced incidence of non-melanoma skin cancer.
| S-EPMC8475539 | biostudies-literature
Project description:BackgroundWhether rosiglitazone may affect the risk of non-melanoma skin cancer (NMSC) has not been investigated.MethodsThe reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 886418 patients with type 2 diabetes were followed up for NMSC incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of rosiglitazone exposure (using tertile cutoffs of duration of therapy and cumulative dose) were calculated and hazard ratios estimated by Cox regression. Additional models were created as sensitivity analyses.ResultsThere were 103097 ever-users and 783321 never-users, respective numbers of incident NMSC 250 (0.24%) and 2084 (0.27%), and respective incidence 68.90 and 76.77 per 100000 person-years. Although the overall hazard ratio was not significant in the unadjusted, age-sex-adjusted or fully adjusted model, the risk was significantly lower in the third tertile of duration of therapy and cumulative dose, with significant P for trends. The fully adjusted hazard ratio (95% confidence interval) for a duration of therapy >13.77 months and a cumulative dose of >1752 mg was 0.723 (0.566, 0.923) and 0.783 (0.618, 0.993), respectively. The findings were supported by various sensitivity analyses.ConclusionsRosiglitazone may reduce the risk of NMSC, but further confirmation is required.
| S-EPMC4325941 | biostudies-literature
Project description:BACKGROUND: Topical 5-fluorouracil 5% cream is one of the treatment modalities for non-melanoma skin cancer (NMSC). There is a lack of suitable therapies to treat patients with extensive NMSC. In this paper we report two patients with extensive NMSC treated by total body application of topical 5-fluorouracil 5% cream. OBSERVATIONS: Topical 5-fluorouracil 5% cream was applied twice daily to the total body, including normal appearing skin. During the treatment, weekly blood samples were taken for measurement of 5-fluorouracil levels. All samples showed a 5-fluorouracil level less than the detection level of 10 microg/l. Total body 5- fluorouracil 5% cream was shown to be an effective treatment in our patients; the majority of lesions cleared in both patients. CONCLUSIONS: In conclusion, total body topical 5- fluorouracil 5% cream application was successful in two patients with extensive NMSC. No detectable serum level of 5-fluorouracil could be determined. Pain and secondary infections were important side effects in our patients. However, in patients with extensive NMSC this treatment may be considered.
| S-EPMC2795156 | biostudies-other
Project description:BackgroundAdult height has been associated with risk of several site-specific cancers, including melanoma. However, less attention has been given to non-melanoma skin cancer (NMSC).MethodsWe prospectively examined the risk of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in relation to adult height in the Nurses' Health Study (NHS, n=117?863) and the Health Professionals Follow-up Study (HPFS, n=51?111). We also investigated the relationships between height-related genetic markers and risk of BCC and SCC in the genetic data sets of the NHS and HPFS (3898 BCC cases, and 8530 BCC controls; 527 SCC cases, and 8962 SCC controls).ResultsAfter controlling for potential confounding factors, the hazard ratios were 1.09 (95% CI: 1.02, 1.15) and 1.10 (95% CI: 1.07, 1.13) for the associations between every 10?cm increase in height and risk of SCC and BCC respectively. None of the 687 height-related single-nucleotide polymorphisms (SNPs) was significantly associated with the risk of SCC or BCC, nor were the genetic scores combining independent height-related loci.ConclusionsOur data from two large cohorts provide further evidence that height is associated with an increased risk of NMSC. More studies on height-related genetic loci and early-life exposures may help clarify the underlying mechanisms.
| S-EPMC5220142 | biostudies-literature