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Advances in Melanoma and Skin Cancers: 2nd Edition
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Advances in Melanoma and Skin Cancers: 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 4546

Special Issue Editors

Dr. Domenico Mallardo

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Guest Editor
Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Institute Nazionale Tumori IRCCS Fondazione "G. Pascale", Via Mariano Semmola, 80131 Naples, Italy
Interests: oncology; translational research of skin cancers; identification of prognostic or predictive biomarkers for immunotherapy treatment; study of gene expression profile in patients with skin cancer; analysis of resistance mechanisms of immunotherapy treatment; biochemical and immunological monitoring; study of immunotherapy treatments in solid tumors; combination strategies with I-O
Special Issues, Collections and Topics in MDPI journals
Dr. Debora Basile

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Guest Editor
Department of Oncology, San Bortolo General Hospital, ULSS 8 Berica-Vicenza, 36100 Vicenza, Italy
Interests: cancer; Immunotherapy; melanoma
Dr. Maria Grazia Vitale

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Guest Editor
Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, National Cancer Institute IRCCS Fondazione “G. Pascale”, Via Mariano Semmola, 80131 Naples, Italy.
Interests: skin cancers; immunotherapy; melanoma; solid tumors; immune mechanisms from Sars-CoV-2 infection in cancer patients

Special Issue Information

Dear Colleagues,

Malignant melanoma is the most aggressive skin cancer, with a high potential for relapse and metastasization. Treatment with classic chemotherapy drugs has a response rate of 10% and a short survival. The availability of immune checkpoint inhibitors (ICIs) has radically changed the prognosis not only in melanoma but also in the majority of skin cancers. Indeed, immunotherapy is currently considered the standard of care as an adjuvant therapy in high-risk resected stage III or IV melanoma, and it also demonstrates excellent results in other skin cancers. Despite these important advances, a large subgroup of patients do not respond to treatment, or relapse due to the onset of primary or acquired resistance, resulting in treatment failure in approximately 50% of patients. Therefore, it is necessary to identify specific biomarkers capable of predicting the clinical benefit of immunotherapy in melanoma and skin cancer patients.

The purpose of this Special Issue is to report the resistance mechanisms and prognostic/predictive molecular markers of immunotherapy treatment in patients with skin cancers. Original research, reviews, and short communication articles mainly focusing on the molecular basis of and advances in skin cancer immunotherapy are welcome. 

Dr. Domenico Mallardo
Dr. Debora Basile
Dr. Maria Grazia Vitale
Guest Editors

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Keywords

  • melanoma
  • immunotherapy
  • biomarkers
  • translational research
  • drug repurposing
  • clinical outcome
  • prognostic markers
  • predictive markers
  • combination immunotherapy

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Published Papers (4 papers)

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Research

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19 pages, 3358 KiB  
Article
Evaluation of a Norcantharidin Nanoemulsion Efficacy for Treating B16F1-Induced Melanoma in a Syngeneic Murine Model
by Gabriel Martínez-Razo, Patrícia C. Pires, Angélica Avilez-Colin, María Lilia Domínguez-López, Francisco Veiga, Eliezer Conde-Vázquez, Ana Cláudia Paiva-Santos and Armando Vega-López
Int. J. Mol. Sci. 2025, 26(3), 1215; https://doi.org/10.3390/ijms26031215 - 30 Jan 2025
Viewed by 777
Abstract
Melanoma, a lethal type of cancer originating from melanocytes, is the leading cause of death among skin cancers. While surgical excision of the lesions is the primary treatment for melanoma, not all cases are candidates for surgical procedures. New treatments and complementary options [...] Read more.
Melanoma, a lethal type of cancer originating from melanocytes, is the leading cause of death among skin cancers. While surgical excision of the lesions is the primary treatment for melanoma, not all cases are candidates for surgical procedures. New treatments and complementary options are necessary, given the increasing diagnosis rate. In the present study, a norcantharidin-containing nanoemulsion was developed and evaluated in vivo using a syngeneic graft murine model. Norcantharidin is the demethylated analog of cantharidin, known for its anticancer properties. Our model contemplates surgical excision surgery simulating the standard treatment and the role of the nanoemulsion as a potential adjuvant therapy. We observed a significant decrease in the growth rate of the melanoma lesion in the treated groups compared to the control group, both at the 20th and 30th days of treatment. Moreover, we evaluated the drug bioavailability in serum samples, and the results showed that norcantharidin was detectable in a range of 0.1 to 0.18 mg/mL in the treated groups. Furthermore, histopathological analysis was performed on the amputated tumors, where significant differences were found regarding size, mitosis rate, lymphocytic infiltration, and multispectral quantitative image analysis compared to the control group. If more clinical studies are conducted, the norcantharidin-containing nanoemulsion could be a potential alternative or adjuvant therapy. Topical nanosystems can become or complement standard therapies, which is needed as melanoma affects not only in terms of mortality but also the patient’s morbidity and life quality. Full article
(This article belongs to the Special Issue Advances in Melanoma and Skin Cancers: 2nd Edition)
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12 pages, 2456 KiB  
Article
ICOSLG Is Associated with Anti-PD-1 and Concomitant Antihistamine Treatment Response in Advanced Melanoma
by Domenico Mallardo, Mario Fordellone, Margaret Ottaviano, Giuseppina Marano, Maria Grazia Vitale, Mario Mallardo, Mariagrazia Capasso, Teresa De Cristofaro, Mariaelena Capone, Teresa Meinardi, Miriam Paone, Patrizia Sabatelli, Rosaria De Filippi, Alessandra Cesano, Ernesta Cavalcanti, Corrado Caracò, Sarah Warren, Alfredo Budillon, Ester Simeone and Paolo Antonio Ascierto
Int. J. Mol. Sci. 2024, 25(22), 12439; https://doi.org/10.3390/ijms252212439 - 19 Nov 2024
Viewed by 2028
Abstract
We previously demonstrated that patients with metastatic unresectable stage IIIb–IV melanoma receiving cetirizine (a second-generation H1 antagonist antihistamine) premedication with immunotherapy had better outcomes than those not receiving cetirizine. In this retrospective study, we searched for a gene signature potentially predictive of the [...] Read more.
We previously demonstrated that patients with metastatic unresectable stage IIIb–IV melanoma receiving cetirizine (a second-generation H1 antagonist antihistamine) premedication with immunotherapy had better outcomes than those not receiving cetirizine. In this retrospective study, we searched for a gene signature potentially predictive of the response to the addition of cetirizine to checkpoint inhibition (nivolumab or pembrolizumab with or without previous ipilimumab). Transcriptomic analysis showed that inducible T cell costimulator ligand (ICOSLG) expression directly correlated with the disease control rate (DCR) when detected with a loading value > 0.3. A multivariable logistic regression model showed a positive association between the DCR and ICOSLG expression for progression-free survival and overall survival. ICOSLG expression was associated with CD64, a specific marker of M1 macrophages, at baseline in the patient samples who received cetirizine concomitantly with checkpoint inhibitors, but this association was not present in subjects who had not received cetirizine. In conclusion, our results show that the clinical advantage of concomitant treatment with cetirizine during checkpoint inhibition in patients with malignant melanoma is associated with high ICOSLG expression, which could predict the response to immune checkpoint inhibitor blockade. Full article
(This article belongs to the Special Issue Advances in Melanoma and Skin Cancers: 2nd Edition)
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Review

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16 pages, 276 KiB  
Review
Current Treatment Paradigms for Advanced Melanoma with Brain Metastases
by Elisabetta Bonzano, Stefania Barruscotti, Silvia Chiellino, Benedetta Montagna, Chiara Bonzano, Ilaria Imarisio, Sara Colombo, Francesco Guerrini, Jessica Saddi, Salvatore La Mattina, Carlo Francesco Tomasini, Giannantonio Spena, Paolo Pedrazzoli and Andrea Lancia
Int. J. Mol. Sci. 2025, 26(8), 3828; https://doi.org/10.3390/ijms26083828 - 18 Apr 2025
Viewed by 459
Abstract
The therapeutic management of melanoma brain metastases has undergone a profound revolution during recent decades. Optimal integration of systemic therapies with local treatments seems to represent the strategy to pursue in order to maximize clinical outcomes, stressing the need for real multidisciplinary care [...] Read more.
The therapeutic management of melanoma brain metastases has undergone a profound revolution during recent decades. Optimal integration of systemic therapies with local treatments seems to represent the strategy to pursue in order to maximize clinical outcomes, stressing the need for real multidisciplinary care in this setting of patients. However, the current approach in the clinics does not necessarily reflect what the current guidelines state, and several pending issues are present, from the ideal therapeutic sequence between stereotactic radiosurgery (SRS) and drug administration to the current role of surgery and whole brain radiotherapy (WBRT), all of which need to be addressed. This narrative review aims to provide practical help for navigating the current controversies, with an eye towards possible future advancements in the field, which could help to obtain a comprehensive molecular characterization of the tumor and a more personalized patient-centered therapeutic approach. Full article
(This article belongs to the Special Issue Advances in Melanoma and Skin Cancers: 2nd Edition)
12 pages, 255 KiB  
Review
Opportunities for Discovery Using Neoadjuvant Immune Checkpoint Blockade in Melanoma
by Uma Nair, Emily Rakestraw, Georgia M. Beasley and Margaret H. O’Connor
Int. J. Mol. Sci. 2025, 26(6), 2427; https://doi.org/10.3390/ijms26062427 - 8 Mar 2025
Viewed by 616
Abstract
Treatment of resectable advanced-stage melanoma with neoadjuvant immunotherapy is rapidly becoming the new standard of care due to significant improvements in event-free survival (EFS) compared to surgery first followed by immunotherapy. The level of responsiveness seen in patients receiving immune checkpoint inhibitors (ICIs) [...] Read more.
Treatment of resectable advanced-stage melanoma with neoadjuvant immunotherapy is rapidly becoming the new standard of care due to significant improvements in event-free survival (EFS) compared to surgery first followed by immunotherapy. The level of responsiveness seen in patients receiving immune checkpoint inhibitors (ICIs) must be mechanistically understood not only for the standardization of treatment but also to advance the novel concept of personalized cancer immunotherapy. This review aims to elucidate markers of the tumor microenvironment (TME) and blood that can predict treatment outcome. Interestingly, the canonical proteins involved in the molecular interactions that immunotherapies aim to disrupt have not been consistent indicators of treatment response, which amplifies the necessity for further research on the predictive model. Other major discussions surrounding neoadjuvant therapy involve the higher-level investigation of ICI efficacy due to the ability to examine a post-treatment tumor molecularly and pathologically, which this review will also cover. As neoadjuvant ICI becomes the standard of care in advanced melanoma treatment, further research aiming to identify more predictive biomarkers of treatment response to advance medical decision-making and patient care should continue to be sought after. Full article
(This article belongs to the Special Issue Advances in Melanoma and Skin Cancers: 2nd Edition)
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