Skin Cancer Melanoma Advance Research

Abstract

Melanoma is the most deadly type of skin cancer, and its morbidity and fatality rates are rising globally. Melanoma has significant heterogeneity and a high potential for metastasis, which limits the effectiveness of currently available treatments, which were limited to chemotherapy, radiation, and surgery for several years. The creation of novel treatment classes, including immune checkpoint and small molecule kinase inhibitors, has been made possible by advances in our understanding of the pathophysiological mechanisms underlying the illness. Effectiveness is still far from ideal, despite the undeniable improvements in patients\' quality of life and survival rates. The primary obstacles are a few negative side effects and resistance mechanisms.As a result, numerous clinical trials looking into novel medications and/or combinations have been prompted by the quest for better alternatives. Drugs\' poor stability, quick metabolism, and limited water solubility restrict the clinical potential and medicinal applications of certain substances. Therefore, the investigation of nanotechnology-based approaches is being investigated as the foundation for the widespread use of various nanosystem types in melanoma treatment. The difficulties in comprehending the mechanisms that increase the effectiveness of these nanosystems will be the main focus of future research.

Introduction

Overview

Melanoma is a highly aggressive but less common form of skin cancer originating from melanocytes, pigment-producing cells. While cutaneous melanoma accounts for most cases, melanocytes also exist in the eyes, mucosal surfaces, and CNS, allowing non-cutaneous melanomas to arise as well. Despite its lower incidence compared to other skin cancers, melanoma causes the most deaths, making it a major public health concern.

I. Classification of Melanoma

Cutaneous Subtypes

1. Superficial Spreading Melanoma (SSM) – Most common (≈70%); arises from pre-existing moles.

2. Nodular Melanoma (NM) – Second most common (15–30%); highly aggressive and fast-growing.

3. Lentigo Maligna Melanoma (LMM) – Occurs in older, fair-skinned individuals; slow-spreading.

4. Acral Lentiginous Melanoma (ALM) – Found on palms, soles, nail beds; more common in darker-skinned individuals.

Other Forms

• Mucosal Melanoma – Rare (<1%), occurs in mucous membranes (e.g., nasal, gastrointestinal).

• Ocular Melanoma

  • Uveal Melanoma – Affects iris, ciliary body, and choroid.

  • Conjunctival Melanoma – Appears as raised lesions on the eye surface.

II. Etiology & Risk Factors

Melanoma is caused by a combination of:

• Environmental factors: UV radiation (natural or artificial tanning), viral infections (e.g., HPV, HIV).

• Genetic predispositions: Mutations in CDKN2A, BAP1, MDM2, and telomere maintenance genes.

• Hereditary conditions: FAMMM syndrome, xeroderma pigmentosum.

• Immunosuppression: Increased risk in AIDS and transplant patients.

III. Biology & Pathogenesis

• Melanoma results from genetic and epigenetic alterations that disrupt normal melanocyte function.

• Key biological traits include resistance to apoptosis, uncontrolled growth, invasion, angiogenesis, and immune evasion.

• Pathogenic mutations often affect tumor suppressor genes or activate oncogenes.

IV. History

• First described by Dr. William Norris in the 1820s, who suggested heredity and recommended wide surgical excision.

• Modern classification and prognosis tools include Clark’s level and Breslow’s depth (tumor thickness).

V. Prognosis & Survival

• 5-year survival for Stage IV melanoma is only ~30%.

• Survival depends on: stage at diagnosis, tumor thickness, ulceration, lymph node involvement, and presence of metastases.

• Early detection (e.g., via skin checks) significantly improves outcomes.

VI. Symptoms

• Common signs include:

  • A new or changing mole

  • Non-healing skin lesions

  • Bleeding or oozing moles

  • Dark spots in the eyes or visual disturbances

VII. Diagnosis and Research

• Systematic literature reviews and research using deep learning (DNNs) are improving melanoma detection via medical imaging.

• Melanoma research now includes AI-powered diagnostic tools to support earlier identification.

VIII. Treatment

1. Surgical Treatment

• Wide local excision is standard for localized melanoma.

• Sentinel lymph node biopsy (SLNB) helps stage the disease and guide treatment.

2. Systemic Therapies

• Immunotherapy: Anti-PD-1 drugs (e.g., nivolumab) have improved outcomes but recurrence still occurs in ~25–30% of cases.

• Combination immunotherapy (e.g., anti-PD-1 + ipilimumab) may benefit patients resistant to single-agent therapy.

• Targeted therapy: Chosen based on genetic mutations like BRAF.

3. Treatment Algorithms

• Modern care uses personalized treatment plans based on:

  • BRAF mutation status

  • Brain metastases

  • Performance status

• Clinical algorithms help guide therapy selection.

IX. Challenges and Outlook

• Mucosal and ocular melanomas have poorer prognoses than cutaneous types.

• Early diagnosis, genetic counseling, and personalized care are critical.

• Continued research is focused on:

  • Improving AI-assisted diagnostics

  • Developing more effective immunotherapies

  • Identifying biomarkers for resistance and prognosis

Conclusion

UV radiation from sunshine is the main environmental risk factor for the development of melanoma skin cancer (4–6). The increased risk of melanoma from sun exposure is tightly associated with UV intensity, and more especially, the UV-B spectrum (5). Moreover, a number of studies have connected a higher risk of melanoma to the timing and patterns of sun exposure. In particular, a chronic, continuous pattern of sun exposure is more frequently associated with actinic keratosis and non-melanoma skin cancers, whereas intense and intermittent sun exposure, which is typical of sunburn histories, is associated with a higher risk. Melanoma is a major public health issue these days. Thousands of people worldwide lose their lives to melanoma every year due to its complexity and unpredictable nature. A few examples of variables linked to elevated risk are age, sex, ethnicity, and personal phenotypic characteristics. However, melanoma is a very avoidable condition. Cancer because UV radiation exposure is the main risk factor. Therefore, it is crucial to invest in the population\'s health literacy. IHC has become more used as an auxiliary test for melanoma diagnosis within the past 20 years. The creation of reliable, sensitive, and targeted cancer biomarkers in the area of Research is still being conducted on tissue immunohistochemistry. Despite its potential as a diagnostic (and even predictive) tool, this approach has drawbacks. Because IHC scoring can be arbitrary, creating diagnostic systems that use several biomarkers will necessitate the concurrent establishment of stringent interpretation standards and standardization protocols to guarantee repeatability across pathologists and between laboratories. Newer, more objective, and repeatable techniques are being developed and have the potential to completely change the way malignancies like melanoma are diagnosed, even though IHC is a helpful method for biomarker recognition. Until the 20th century, when wise clinical observations and developments in molecular biology demonstrated the hereditary basis of melanoma, the disease was still poorly understood and deadly. and environmental elements that contribute to its growth and development. One of the most prevalent and aggressive types of skin cancer nowadays is melanoma, which is also one of the most curable if caught early. The study of mutational profiles was transformed by genomics. From the 1800s until the 2010s, immunotherapies and cytotoxic chemotherapy followed significant advancements in the history of melanoma. Melanoma may have a better future thanks to genetics, which may also lessen the suffering of oncologists who treat largely fatal cases.

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Copyright

Copyright © 2025 Ms. Sarika Lakade, Ms. Rekha Kolape, Mr. Nitin Gawai, Mr. Prathamesh Gaikwad, Ms. Shweta Navale, Ms. Madhavi Kudale. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.