Molecular Alterations in Cutaneous Squamous Cell Carcinoma in Immunocompetent and Immunosuppressed Hosts—A Systematic Review

Tsang, Denise Ann; Tam, Steve Yew Chong; Oh, Choon Chiat

doi:10.3390/cancers15061832

Cited by 5 publications

(5 citation statements)

References 110 publications

(157 reference statements)

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“…36,44,45 Given distinct differences in the molecular alterations and TME characteristics of tumours of immunocompromised compared to immunocompetent patients, comprehensive screening of both cohorts is critical. 46,47 Further, none are derived from a female; while males are more predominately affected by metastatic cSCC, there is increasing suggestion of a sex-related influence on disease progression requiring greater preclinical representation. 48,49 These limitations are compounded by the time to establish these cell lines by clonal outgrowth, followed by a minimum of four but usually beyond 10 passages.…”

Section: Improving Model S Of Me Ta S Tati C C Sccmentioning

confidence: 99%

“…Only one cell line, MET4, is taken from an immunocompromised patients' tumour, undermining the clinical trend of a high disease burden and distinct immunological‐associated mutational signature in this cohort 36,44,45 . Given distinct differences in the molecular alterations and TME characteristics of tumours of immunocompromised compared to immunocompetent patients, comprehensive screening of both cohorts is critical 46,47 . Further, none are derived from a female; while males are more predominately affected by metastatic cSCC, there is increasing suggestion of a sex‐related influence on disease progression requiring greater preclinical representation 48,49 .…”

Section: Improving Models Of Metastatic Csccmentioning

confidence: 99%

See 1 more Smart Citation

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Conley,

Perry,

Ashford

et al. 2024

Experimental Dermatology

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Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy worldwide, with most deaths caused by locally advanced and metastatic disease. Treatment of resectable metastases is typically limited to invasive surgery with adjuvant radiotherapy; however, many patients fail to respond and there is minimal data to predict response or propose effective alternatives. Precision medicine could improve this, though genomic biomarkers remain elusive in the high mutational background and genomic complexity of cSCC. A phenotypic approach to precision medicine using patient‐derived ex vivo tumour models is gaining favour for its capacity to directly assess biological responses to therapeutics as a functional, predictive biomarker. However, the use of ex vivo models for guiding therapeutic selection has yet to be employed for metastatic cSCC. This review will therefore evaluate the existing experimental models of metastatic cSCC and discuss how ex vivo methods could overcome the shortcomings of these existing models. Disease‐specific considerations for a prospective methodological pipeline will also be discussed in the context of precision medicine.

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Section: Improving Model S Of Me Ta S Tati C C Sccmentioning

confidence: 99%

Section: Improving Models Of Metastatic Csccmentioning

confidence: 99%

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Conley,

Perry,

Ashford

et al. 2024

Experimental Dermatology

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“…Epigenetic changes may occur as well [ 19 , 20 ]. However, complete understanding of molecular changes in cSCC has not been achieved yet [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular and Histopathological Characterization of Metastatic Cutaneous Squamous Cell Carcinomas: A Case–Control Study

Paganelli,

Zaffonato,

Donati

et al. 2024

Cancers

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Background: A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The study aims to identify specific histological and molecular parameters characterizing metastatic cSCC. Methods: Patients affected by metastatic and non-metastatic cSCC (controls) were included in the present study and matched for clinical and histological characteristics. Skin samples from primary tumors were revised for several histological parameters and also underwent gene expression profiling with a commercially available panel testing 770 different genes. Results: In total, 48 subjects were enrolled in the study (24 cases, 24 controls); 67 genes were found to be differentially expressed between metastatic and non-metastatic cSCC. Most such genes were involved in immune regulation, skin integrity, angiogenesis, cell migration and proliferation. Conclusion: The combination of histological and molecular profiles of cSCCs allows the identification of features specific to metastatic cSCC, with potential implications for more precise patient risk stratification.

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“…Several molecular pathways are implicated in the development of cSCC, including mutations in the P53 gene, alterations in suppressor genes such as CDKN2A and NOTCH, oncogenes such as RAS, and activation of the NF-kB, MAPK, and PI3K/AKT/mTOR pathways. In addition to genetic mutations, epigenetic changes can also play a role in this process [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Expression Levels of Epidermal Growth Factor Receptor, Cyclooxygenase-2, and Ki-67 in Canine Cutaneous Squamous Cell Carcinomas

Luís,

Files,

Cardoso

et al. 2024

CIMB

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Squamous cell carcinoma (SCC) stands as the second most prevalent skin cancer in dogs, primarily attributed to UV radiation exposure. Affected areas typically include regions with sparse hair and pale or depigmented skin. The significance of spontaneous canine cutaneous SCC as a model for its human counterpart is underscored by its resemblance. This study assesses the expression of key markers—Epidermal Growth Factor Receptor (EGFR), Cyclooxygenase-2 (Cox-2), and Ki-67—in canine cutaneous SCC. Our objective is to investigate the association between their expression levels and classical clinicopathological parameters, unraveling the intricate relationships among these molecular markers. In our retrospective analysis of 37 cases, EGFR overexpression manifested in 43.2% of cases, while Cox-2 exhibited overexpression in 97.3%. The EGFR, Cox-2 overexpression, and Ki-67 proliferation indices, estimated through immunohistochemistry, displayed a significant association with the histological grade, but only EGFR labeling is associated with the presence of lymphovascular emboli. The Ki-67 labeling index expression exhibited an association with EGFR and Cox-2. These findings propose that EGFR, Cox-2, and Ki-67 hold promise as valuable markers in canine SCC. EGFR, Cox-2, and Ki-67 may serve as indicators of disease progression, offering insights into the malignancy of a lesion. The implications extend to the potential therapeutic targeting of EGFR and Cox-2 in managing canine SCC. Further exploration of these insights is warranted due to their translational relevance and the development of targeted interventions in the context of canine SCC.

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Molecular Alterations in Cutaneous Squamous Cell Carcinoma in Immunocompetent and Immunosuppressed Hosts—A Systematic Review

Cited by 5 publications

References 110 publications

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Molecular and Histopathological Characterization of Metastatic Cutaneous Squamous Cell Carcinomas: A Case–Control Study

Immunohistochemical Expression Levels of Epidermal Growth Factor Receptor, Cyclooxygenase-2, and Ki-67 in Canine Cutaneous Squamous Cell Carcinomas

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