scholarly journals Pharmacologically Induced Cutaneous Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Natalia García
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Clinical Behavior ◽  
Mutational Burden ◽  
Therapeutic Landscape ◽  
Increased Risk

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise. Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic. The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape. Several drugs have been developed for CSCC treatment, but the disease may actually be induced by drugs as well. Molecular mechanisms underlie pharmacologically-induced CSCC, and a sound knowledge of them could help physicians better tackle this tumor. 

scholarly journals Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

2020 ◽  
Vol 21 (8) ◽  
pp. 2956 ◽  
Author(s):  
Roberto Corchado-Cobos ◽  
Natalia García-Sancha ◽  
Rogelio González-Sarmiento ◽  
Jesús Pérez-Losada ◽  
Javier Cañueto
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Basis ◽  
Checkpoint Inhibitors ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Drug Induced ◽  
Mutational Burden ◽  
Therapeutic Landscape ◽  
Increased Risk

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise. Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic. The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape. This review focuses on the molecular basis of CSCC and the current biology-based approaches of targeted therapies and immune checkpoint inhibitors. Another purpose of this review is to explore the landscape of drugs that may induce or contribute to the development of CSCC. Beginning with the pathogenetic basis of these drug-induced CSCCs, we move on to consider potential therapeutic opportunities for overcoming this adverse effect.

Successful use of immunotherapy to treat advanced cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa

2021 ◽  
Vol 14 (2) ◽  
pp. e238966
Author(s):  
Tony Duong ◽  
Debra Wong ◽  
Alexander Barrett ◽  
Harper Price
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epidermolysis Bullosa ◽  
Checkpoint Inhibitors ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Dystrophic Epidermolysis Bullosa ◽  
Mutational Burden ◽  
Increased Risk ◽  
Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is a multisystem inherited disorder associated with fragile skin, blister formation and poor wound healing. Patients with RDEB are at significantly increased risk of recurrent and aggressive cutaneous squamous cell carcinoma (cSCC) and because of their disease complexity, conventional therapies may not be possible. Recent advances in cancer immunotherapy have led to the successful use of immune checkpoint inhibitors (ICIs) in melanoma and other malignancies. However, the effects of ICIs in patients with cSCC and RDEB are currently unknown. A 30-year-old woman with RDEB and multiple unresectable cSCCs was found to have high tumour mutational burden and PD-L1 (programmed cell death-ligand 1) expression. She was started on an ICI, which yielded disease control and was well tolerated. Furthermore, her RDEB wounds improved. This case demonstrates successful use of immunotherapy for advanced cSCC in RDEB, a disease that is often challenging to treat with local therapies.

scholarly journals Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma

2016 ◽  
Vol 152 (5) ◽  
pp. 527 ◽  
Author(s):  
Shalini V. Mohan ◽  
Julia Chang ◽  
Shufeng Li ◽  
A. Solomon Henry ◽  
Douglas J. Wood ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Basal Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Increased Risk

scholarly journals Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Suttichai Krisanaprakornkit ◽  
Anak Iamaroon
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Large Body ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition

Oral cancer is one of the drastic human cancers due to its aggressiveness and high mortality rate. Of all oral cancers, squamous cell carcinoma is the most common accounting for more than 90%. Epithelial-mesenchymal transition (EMT) is suggested to play an important role during cancer invasion and metastasis. Recently, emerging knowledge on EMT in carcinogenesis is explosive, tempting us to analyze previous studies on EMT in oral squamous cell carcinoma (OSCC). In this paper, we have first addressed the general molecular mechanisms of EMT, evidenced by alterations of cell morphology during EMT, the presence of cadherin switching, turning on and turning off of many specific genes, the activation of various signaling pathways, and so on. The remaining part of this paper will focus on recent findings of the investigations of EMT on OSCC. These include the evidence of EMT taking place in OSCC and the signaling pathways employed by OSCC cells during their invasion and metastasis. Collectively, with the large body of new knowledge on EMT in OSCC elaborated here, we are hopeful that targeting treatment for OSCC will be developed.

Association of tumor mutational burden in cutaneous squamous cell carcinoma with genomic alterations in Notch family receptors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13031-e13031
Author(s):  
Eric Allan Severson ◽  
Shakti Ramkissoon ◽  
Sugganth Daniel ◽  
Jo-Anne Vergilio ◽  
Laurie M. Gay ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Family Member ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Genomic Alterations ◽  
Functional Impact ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Frameshift Indels

e13031 Background: In Cutaneous Squamous Cell Carcinoma (cSqCC), Notch1, Notch2, and Notch3 have been identified as tumor suppressors with a high rate of inactivating mutations early in cSqCC pathogenesis. Despite the high frequency of alterations, the biologic and therapeutic implications of Notch genomic alterations (GAs) in cSqCC are incompletely understood. Methods: 232 FFPE samples of cSqCC were evaluated by comprehensive genomic profiling (CGP) of 315 genes and analyzed for all classes of GAs, with diagnoses confirmed by central pathology review. Notch GAs with unknown functional impact were excluded. Tumor mutational burden (TMB) was calculated from 1.11 Mb of sequenced DNA and reported as mutations/Mb. Results: The cohort of 232 samples was 78% male and 22% female, aged from 17 to 88, with confirmed metastatic disease in 32% of cases. 115 (50%) samples had a Notch family member GA with a known or predicted functional impact. 96 cases had Notch1 GAs, 43 cases had Notch2 GAs, and 14 cases had Notch3 GAs with 40 cases having GAs in multiple Notch family members. These mutations were 41% missense, 34% nonsense, 15% splice site, 9% frameshift indels, and 1% non-frameshift indels alterations. Patients with Notch GAs were significantly older (median 70 years old vs median 64, p < 0.01). TMB was increased among samples with Notch GAs (median TMB of 63 mutations/mb versus 20 mutations/mb, p < 1x10-6), with similar differences for primary and metastatic samples. Cases with Notch GAs had more total GAs per case (mean 10.4 vs 7.4, p < 1.5x10-10); however, the top co-mutated genes were the same (TP53, CDKN2A, FAT1, MLL2). Both groups had a high proportion of C- > T/G- > A transitions, consistent with UV damage; however, the proportion was higher in cases with Notch GAs (median 83% vs 80%) - a difference seen in primary and metastatic samples. Conclusions: 50% of cSqCC cases had a Notch family member loss of function GA, which was associated with increased TMB in the primary and metastatic setting. With pre-clinical models and case studies showing responses to PD-1 inhibitors in cSqCC, further investigations are warranted into the associations of Notch GAs with mutational burden and response to immunotherapy.

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