Current Pharmaceutical Design - Volume 32, Issue 4, 2026

Skin cancer is broadly classified into two categories i.e., non-melanoma skin cancer (NMSC) and malignant melanoma (MM), with MM having a greater fatality rate than NMSC. A large number of treatment strategies currently exist for these skin cancer types, ranging from monotherapies to complex multifaceted synergistic interventions including dual therapies, trimodality therapy, and multicomponent combinations therapy. These combinatorial cancer treatments have delivered more favorable results when compared with monotherapies, and although combination treatments increase the cost of treatment, these regimens have lower side effect profiles, decreased resistance, high efficacy and an improved long-term response. Synergistic combination treatments for skin cancer are often complex, wide-ranging and encompass diverse platforms with various mechanisms of action. An understanding of the physiological potential, as well the efficacy of such treatments, is therefore vital to ensure patients receive the best possible treatment. This review therefore focuses on the current advancements and existing non-surgical combinative drug delivery methods utilized for treating skin cancer. It encompasses the diverse pharmaceutical delivery systems, clinical outcomes, and oncology strategies employed and aims to highlight the role of non-surgical combination therapies in enhancing patient compliance, reducing treatment durations, and improving overall survival rates while addressing relapses and metastasis. The promising outlook of the research being conducted in this field has also been provided, as well as the barriers to the effective treatment of this complex condition.

Melanoma brain metastases (MBM) are associated with poor prognosis and remain a significant challenge in oncology. In recent years, significant progress has been made in understanding the molecular mechanisms underlying MBM. Advances in targeted therapies, immunotherapies, and stereotactic radiosurgery (SRS) have significantly improved patient survival. This study presents an overview of the current landscape of treatment approaches and emerging modalities for MBM treatment, highlighting recent advancements and future directions for research and clinical practice.

Mucosal Melanoma (MM) is an aggressive disease that is distinct from cutaneous melanoma in risk factors, prognosis, and treatment. Surgical treatment is currently the treatment of choice for localized disease; however, the recurrence rate is common. For advanced or metastatic disease, immunotherapy with PD-1 inhibitors and anti-CTLA is generally first-line treatment, however the overall responses to immunotherapy in MM are often lower and less robust when compared to that observed in cutaneous melanoma. Adoptive-TIL therapy has shown great promise. Other advances, particularly through the exploration of novel and combination therapies, are a step forward and a hope to improve outcomes in patients with mucosal melanoma. In this review, we summarize current treatment options for MM, and we updated future clinical trials available for this population of patients.

Dermoscopy is a very important diagnostic tool in clinical practice. It increases accuracy in skin cancer detection. Melanoma and its major variants have distinct dermoscopic patterns and structures described as well as cutaneous keratynocytic tumors such as basal cell carcinoma and squamous cell carcinomas. Superficial spreading melanoma may show dermoscopic structures varying from atypical network, atypical hyperpigmentation, atypical globules and dots, and atypical streaks to negative network; lentigo maligna lesions demonstrate dermoscopic structures associated with the tumour progression around follicular openings; nodular lesions may be suspected mainly by colors (pink or blue and black) and the recognition of peculiar patterns such as the parallel ridge pattern may facilitate vascular structures and acral lentiginous. The histopathologic subtype of BCC is an important determinant of the dermoscopic pattern of the tumor, being the vascular strucutures a significant clue for its diagnosis. Invasive squamous cell carcinoma may also be differentiated from in situ lesions by clinical and dermoscopic aspects such as vascular and hyperkeratotic structures. The aim of this review was to provide a comprehensive overview of the major dermoscopic patterns and structures described for the diagnosis of major melanoma variants and for cutaneous carcinomas. It also gives some insights about sequential digital imaging for patients with multiple melanocytic nevi.

Although cutaneous melanoma accounts for only about 2% of skin cancers, its rapid progression makes it an aggressive skin cancer with a high mortality rate. As of 2018, the SEER database estimated that the 5-year overall survival (OS) rate is 29.8% in patients with stage IV disease at diagnosis in the United States. Non-cutaneous melanoma, including mucosal and uveal subtypes, carries a generally worse prognosis. Once considered refractory to conventional treatments, such as chemotherapy and radiation therapy, the advent of immunotherapy, including immune checkpoint inhibitors (ICIs), vaccines, and tumor-infiltrating lymphocytes (TIL), and of targeted therapy over the past decade has resulted in dramatic improvements in melanoma. Importantly, ICIs have resulted in long-term remission for patients with melanoma, thus introducing the possibility of a cure for some patients with metastatic disease. These include antibodies against programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and lymphocyte activation gene-3 (LAG-3). In this review, we will provide an overview of metastatic melanoma while focusing on its current pharmacologic armamentarium, toxicities of treatment, including ICIs and targeted therapy, and its therapeutic clinical strategies. The therapeutic advances presented in this review serve as the foundation for an ever-expanding repertoire of innovative approaches. These include mRNA vaccines, oncolytic viruses, bispecific engagers, oral immunomodulators, and novel cytokines. Adoptive cellular strategies are evolving to TILS transduced with conditional gene expression cassettes, as well as non-T cell approaches involving dendritic cells and natural killer (NK) cells. Targeted therapy strategies have broadened to include upstream components of RAS, other MAP kinase pathways, and HDAC inhibitors, among others. All these new paradigms translate into increasingly complex decision-making for the treatment team, a burden that is more than offset by the tremendous benefit for melanoma patients. This is truly the beginning of a new era.