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 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 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 Treatment of Cutaneous Squamous Cell Carcinoma with Immune Checkpoint Inhibitors in Special Populations

2021 ◽  
Vol 11 (S2) ◽  
pp. e2021170S
Author(s):  
Paolo Bossi ◽  
Luigi Lorini
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Current Evidence ◽  
Special Populations ◽  
Solid Organ

Cutaneous squamous cell carcinoma (cSCC) may develop in patients with dysregulated immune activation (pre-existing autoimmune diseases or immunosuppression due to hematopoietic/solid organ transplant recipients), patients with a compromised immune function (long-term immunosuppression), and patients carrying chronic viral infections, or those affected by lymphoproliferative diseases. It should be also considered that patients presenting with immunosuppression have a high incidence of cSCC (65–250-times higher than general population), highlighting the central role played by the immune system in the development of cSCC. All these cases must be considered as “special populations” for treatment with immune checkpoint inhibitors (ICIs), as the safety and activity of these drugs have not been studied on these specific cases, since these patients were excluded from clinical trials leading to approval of ICIs. It is therefore important to gain as much information as possible from the analysis of real-life data, to derive an indication to be adopted in everyday clinical setting.  Moreover, therapeutic alternatives other than ICIs are scarce, mainly consisting in chemotherapy and anti-EGFR agents, whose activity is lower than immunotherapy and whose toxicity (particularly with chemotherapy) are not sustainable by this frail population. Here, we describe the current evidence of treatment with ICIs in special populations and conclude that it is necessary to find a balance between treatment risks (toxicities) and benefits (efficacy), as well as engaging a multidisciplinary team of experts to thoroughly manage and treat these patients.

Targeted Therapy and Traditional Chemotherapy in Melanoma and Cutaneous Squamous Cell Carcinoma

2020 ◽  
Vol 36 (02) ◽  
pp. 186-193 ◽  
Author(s):  
Vincent T. Ma ◽  
Catherine T. Haring ◽  
Govind Warrier ◽  
Paul L. Swiecicki
Keyword(s):  
Squamous Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Relevant Literature ◽  
Cancer Therapeutics ◽  
Cytotoxic Chemotherapy ◽  
Cutaneous Squamous Cell Carcinoma

AbstractCutaneous squamous cell carcinoma (cSCC) and melanoma encompass the majority of all malignant skin cancers. There has been an increase in their incidence globally in recent decades. In cases of high-risk, unresectable, or metastatic disease; or when patient factors or preferences limit the availability of conventional surgery or radiotherapy; or a systemic therapy is often warranted. Our improved understanding of the molecular and immune pathogenesis underlying tumor growth and development has been critical in advancing cancer therapeutics. Over the past several years, several new systemic agents have been approved for both diseases. The role of cytotoxic chemotherapy is gradually waning with the introduction of targeted therapy and immunotherapy. In this article, we review the current and relevant literature and evidence of cytotoxic chemotherapy, targeted therapy, and immune checkpoint inhibitors in the adjuvant and neoadjuvant settings for cSCC and melanoma. Additionally, we describe their role in the unresectable or metastatic disease setting.

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.

Immune checkpoint inhibitors for treatment of periorbital squamous cell carcinoma

2021 ◽  
pp. bjophthalmol-2021-319417
Author(s):  
Jeremy Allan Goldfarb ◽  
Renata Ferrarotto ◽  
Neil Gross ◽  
Ryan Goepfert ◽  
James Matthew Debnam ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Chart Review ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Retrospective Chart Review ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Therapeutic Outcomes

PurposeTo report on the outcomes of immunotherapy in patients with locally advanced periorbital squamous cell carcinoma.MethodsWe performed a retrospective chart review of seven consecutive patients with locally advanced periorbital cutaneous squamous cell carcinoma treated with anti-PD-1 immunotherapy. Treatments and therapeutic outcomes were reviewed.ResultsOf the seven patients, six were treated with cemiplimab, and one was treated with pembrolizumab. Five patients were treated with immunotherapy as neoadjuvant therapy before planned surgical resection; two patients received immunotherapy for treatment of advanced recurrent lesions deemed unresectable following multiple previous excisions and radiation therapy. In all seven patients, measurable clinical and/or radiologic response was observed.ConclusionsOur findings support the emerging role of anti-PD-1 immunotherapy in the management of locally advanced periorbital cutaneous squamous cell carcinoma.

Sign in / Sign up

Export Citation Format

Share Document