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Research Progress of Cutaneous Squamous and Basal Cell Carcinomas (Volume...
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Research Progress of Cutaneous Squamous and Basal Cell Carcinomas (Volume II)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 4932

Special Issue Editors

Dr. Moran Amit

E-Mail Website
Guest Editor
Department of Head and Neck Surgery, Division of Surgery, MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: cancer; neuroscience; tumor microenvironment; immunotherapy; head and neck
Special Issues, Collections and Topics in MDPI journals
Dr. Frederico O. Gleber-Netto

E-Mail Website
Guest Editor
Department of Head and Neck Surgery, Division of Surgery, MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: translational research; cancer genomics; squamous cell carcinoma; biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Neil D. Gross

E-Mail Website
Guest Editor
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Centre, Houston, TX 77030, USA
Interests: squamous cell carcinoma; thyroid cancer

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the Special Issue “Research Progress of Cutaneous Squamous and Basal Cell Carcinomas”, available at https://www.mdpi.com/journal/cancers/special_issues/CSCC_cancers.

We are pleased to invite you to contribute to this Special Issue, which aims to explore the relationship between the TIME (tumor immune microenvironment) and the development, progression, and treatment of cSCC.

More than a million new cases of cutaneous squamous cell carcinoma (cSCC) are diagnosed yearly in the USA, and their incidence is expected to increase worldwide as the population ages. As opposed to other nonmelanoma skin cancers, cSCC is associated with an increased rate of distant metastasis and elevated morbimortality.

Immunosuppression is directly related to the risk of cSCC development, and chronically immunosuppressed individuals, such as organ transplant recipients and those with hematological malignancies, represent a significant portion of cSCC patients. Unfortunately, since immunodeficiency is a major risk factor for metastatic dissemination, these vulnerable patients are more prone to developing advanced disease.

Chronic ultraviolet exposure (UV) is a major etiological factor for cSCC and promotes a unique mutation signature in these tumors. It is also an important immunosuppressive agent and may contribute to a reduction in local immunosurveillance, favoring pro-tumorigenic changes such as skin infection by beta human papillomavirus (HPV), which is considered an important promoter of skin carcinogenesis.

Although the relevance of the tumor immune microenvironment (TIME) in the initiation and progression of cSCC is widely accepted, our understanding of the intricate relationship between the TIME and the cSCC is limited. Consequently, the development and application of new measures for the prevention and treatment of cSCC, especially those linked to immunomodulation, require further exploration.

Original research articles and reviews are welcome. We look forward to receiving your contributions.

Dr. Moran Amit
Dr. Frederico O. Gleber-Netto
Dr. Neil D. Gross
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tumor immune microenvironment
  • cutaneous squamous cell carcinoma
  • immunodeficiency
  • biomarkers
  • therapeutics
  • ultraviolet

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Published Papers (5 papers)

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Review

14 pages, 295 KiB  
Review
Current Advances and Challenges in the Management of Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patients
by Sophie Li, Thomas Townes and Shorook Na’ara
Cancers 2024, 16(18), 3118; https://doi.org/10.3390/cancers16183118 - 10 Sep 2024
Viewed by 354
Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and poses a significant risk to immunosuppressed patients, such as solid organ transplant recipients and those with hematopoietic malignancies, who are up to 100 times more likely to develop cSCC compared [...] Read more.
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and poses a significant risk to immunosuppressed patients, such as solid organ transplant recipients and those with hematopoietic malignancies, who are up to 100 times more likely to develop cSCC compared with the general population. This review summarizes the current state of treatment for cSCC in immunosuppressed patients, focusing on prevention, prophylaxis, surgical and non-surgical treatments, and emerging therapies. Preventative measures, including high-SPF sunscreen and prophylactic retinoids, are crucial for reducing cSCC incidence in these patients. Adjusting immunosuppressive regimens, particularly favoring mTOR inhibitors over calcineurin inhibitors, has been shown to lower cSCC risk. Surgical excision and Mohs micrographic surgery remain the primary treatments, with adjuvant radiation therapy recommended for high-risk cases. Traditional chemotherapy and targeted therapies like EGFR inhibitors have been utilized, though their efficacy varies. Immunotherapy, particularly with agents like cemiplimab and pembrolizumab, has shown promise, but its use in immunosuppressed patients requires further investigation due to potential risks of organ rejection and exacerbation of underlying conditions. Treatment of cSCC in immunosuppressed patients is multifaceted, involving preventive strategies, tailored surgical approaches, and cautious use of systemic therapies. While immunotherapy has emerged as a promising option, its application in immunosuppressed populations necessitates further research to optimize safety and efficacy. Future studies should focus on the integration of personalized medicine and combination therapies to improve outcomes for this vulnerable patient group. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas (Volume II))
18 pages, 2316 KiB  
Review
Cutaneous Squamous Cell Carcinoma in Patients with Solid-Organ-Transplant-Associated Immunosuppression
by Karam Khaddour, Naoka Murakami, Emily S. Ruiz and Ann W. Silk
Cancers 2024, 16(17), 3083; https://doi.org/10.3390/cancers16173083 - 4 Sep 2024
Viewed by 744
Abstract
The management of advanced cutaneous squamous cell carcinoma (CSCC) has been revolutionized by the introduction of immunotherapy. Yet, successful treatment with immunotherapy relies on an adequate antitumor immune response. Patients who are solid-organ transplant recipients (SOTRs) have a higher incidence of CSCC compared [...] Read more.
The management of advanced cutaneous squamous cell carcinoma (CSCC) has been revolutionized by the introduction of immunotherapy. Yet, successful treatment with immunotherapy relies on an adequate antitumor immune response. Patients who are solid-organ transplant recipients (SOTRs) have a higher incidence of CSCC compared to the general population. This review discusses the current knowledge of epidemiology, pathophysiology, and management of patients with CSCC who are immunocompromised because of their chronic exposure to immunosuppressive medications to prevent allograft rejection. First, we discuss the prognostic impact of immunosuppression in patients with CSCC. Next, we review the risk of CSCC development in immunosuppressed patients due to SOT. In addition, we provide an overview of the biological immune disruption present in transplanted immunosuppressed CSCC patients. We discuss the available evidence on the use of immunotherapy and provide a framework for the management approach with SOTRs with CSCC. Finally, we discuss potential novel approaches that are being investigated for the management of immunosuppressed patients with CSCC. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas (Volume II))
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15 pages, 1087 KiB  
Review
Therapeutic Advances in Advanced Basal Cell Carcinoma
by Samer Alkassis, Maya Shatta and Deborah J. Wong
Cancers 2024, 16(17), 3075; https://doi.org/10.3390/cancers16173075 - 4 Sep 2024
Viewed by 573
Abstract
Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone. While most cases are treatable with low recurrence rates, 1–10% progress to an advanced stage which can behave aggressively, leading [...] Read more.
Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone. While most cases are treatable with low recurrence rates, 1–10% progress to an advanced stage which can behave aggressively, leading to local destruction and posing substantial challenges in management. The pathogenesis often involves dysregulation of the patched/hedgehog protein family, a pivotal pathway targeted by recently approved therapies. Furthermore, the role of immunotherapy is evolving in this type of tumor as we learn more about tumor microenvironment dynamics. In recent years, there have been advancements in the therapeutic landscape of advanced BCC, offering patients new hope and options for managing this complex and potentially life-threatening condition. In this review, we aim to provide a comprehensive overview of this disease, including the risk factors, underlying pathogenesis, current treatment options of advanced disease, and the ongoing exploration and development of novel therapies. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas (Volume II))
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Figure 1

9 pages, 240 KiB  
Review
Efficacy and Safety of Cemiplimab for the Management of Non-Melanoma Skin Cancer: A Drug Safety Evaluation
by Luca Potestio, Massimiliano Scalvenzi, Aimilios Lallas, Fabrizio Martora, Luigi Guerriero, Luigi Fornaro, Laura Marano and Alessia Villani
Cancers 2024, 16(9), 1732; https://doi.org/10.3390/cancers16091732 - 29 Apr 2024
Cited by 2 | Viewed by 1149
Abstract
Non-melanoma skin cancer includes several types of cutaneous tumors, with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) as the commonest. Among the available therapeutic options, surgical excision is the mainstay of treatment for both tumors. However, tumor features and patients’ [...] Read more.
Non-melanoma skin cancer includes several types of cutaneous tumors, with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) as the commonest. Among the available therapeutic options, surgical excision is the mainstay of treatment for both tumors. However, tumor features and patients’ comorbidities may limit the use of these techniques, making the treatment challenging. As regards BCC, even if hedgehog inhibitors revolutionized the therapeutic scenario, there are still patients unresponsive or intolerant to these drugs. In this context, cemiplimab has been approved as second-line treatment. As regards SCC, cemiplimab was the first systemic therapy approved. The objective of this manuscript was to investigate the efficacy and safety of cemiplimab for the management of BCC and cSCC. Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Different specialists including oncologists, radiologists, dermatologists, and surgeons are required to guarantee an integrated approach, leading to the best management of patients. Moreover, the collaboration among specialists will allow them to best manage the TEAEs, reducing the risk of treatment suspension or discontinuation. Certainly, ongoing studies and more and more emerging real-world evidence, will allow us to better characterize the role of cemiplimab for the management of advanced non-melanoma skin cancer. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas (Volume II))
10 pages, 1105 KiB  
Review
Neoadjuvant Approaches to Non-Melanoma Skin Cancer
by David C. Wilde, Mica E. Glaun, Michael K. Wong and Neil D. Gross
Cancers 2023, 15(23), 5494; https://doi.org/10.3390/cancers15235494 - 21 Nov 2023
Cited by 1 | Viewed by 1580
Abstract
Surgery and external-beam radiation therapy are the primary treatment modalities for locally advanced NMSC, but they can lead to impairment of function and disfigurement in sensitive areas such as the head and neck. With the advent of targeted systemic therapies and immunotherapy, physicians [...] Read more.
Surgery and external-beam radiation therapy are the primary treatment modalities for locally advanced NMSC, but they can lead to impairment of function and disfigurement in sensitive areas such as the head and neck. With the advent of targeted systemic therapies and immunotherapy, physicians have explored the ability to offer neoadjuvant therapy for NMSC in order to reduce surgically induced morbidity. Provided herein is a guide to current applications of neoadjuvant systemic therapies for NMSC and future directions. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas (Volume II))
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