Skin Cancer
Skin cancer is a malignant transformation of skin cells characterized by the uncontrolled proliferation of atypical cells within the epidermis, dermis, or associated appendages. The pathogenesis of skin cancer involves cumulative DNA damage, often induced by ultraviolet (UV) radiation from sunlight or artificial sources, leading to mutations in oncogenes and tumor suppressor genes such as p53. Additional risk factors include genetic predisposition, fair skin phenotype, immunosuppression, exposure to carcinogenic chemicals, and certain viral infections. The health impacts of skin cancer range from localized tissue destruction and cosmetic disfigurement to regional and distant metastasis, particularly in aggressive subtypes, contributing to significant morbidity and, in advanced cases, mortality. Early detection and intervention are critical in reducing disease burden and improving survival outcomes.
Basal cell carcinoma is the most prevalent form of skin cancer, arising from the basal cells located in the lowest layer of the epidermis. BCC typically presents as pearly or translucent nodules, often with telangiectasia, and may ulcerate over time. It is characterized by slow growth and a low propensity for metastasis but can cause extensive local tissue destruction if untreated. Risk factors include chronic sun exposure and genetic syndromes such as basal cell nevus syndrome.
Squamous cell carcinoma originates from the keratinizing cells of the epidermis and is the second most common type of skin cancer. SCC often manifests as scaly, erythematous plaques or nodules that may ulcerate or bleed. It has a higher metastatic potential than BCC, especially when arising on the lips, ears, or in immunocompromised patients. Cumulative UV exposure, chronic wounds, and exposure to carcinogens like arsenic are established risk factors.
Melanoma is a malignant tumor of melanocytes, the pigment-producing cells of the skin. It is less common than BCC and SCC but is responsible for the majority of skin cancer-related deaths due to its aggressive nature and high metastatic potential. Clinically, melanoma may present as an asymmetrical, irregularly bordered, multicolored lesion with evolving characteristics. Risk factors include intense intermittent UV exposure, numerous nevi, family history, and genetic mutations such as BRAF.
Merkel cell carcinoma is a rare but highly aggressive neuroendocrine carcinoma of the skin. It frequently presents as a rapidly growing, painless, firm, bluish-red nodule in sun-exposed areas, predominantly affecting older adults and immunosuppressed individuals. Merkel cell polyomavirus infection is implicated in its pathogenesis, and the tumor is associated with a high risk of recurrence and metastasis.
Skin cancer is the most commonly diagnosed malignancy worldwide, with incidence rates continuing to rise, particularly in fair-skinned populations and regions with high ultraviolet radiation exposure. Basal cell carcinoma accounts for approximately 70-80% of non-melanoma skin cancers, while squamous cell carcinoma comprises 20-25%. Melanoma represents about 1-2% of all skin cancers but is responsible for the majority of skin cancer-related mortality. According to global estimates, over 5 million cases of non-melanoma skin cancer and over 325,000 cases of melanoma are diagnosed annually. The lifetime risk of developing skin cancer varies by geography, phenotype, and behavior, with Australia and New Zealand reporting the highest melanoma rates. Age-standardized mortality rates for melanoma approximate 0.6 per 100,000 globally but are higher in older males and in regions with delayed diagnosis. The increasing prevalence of immunosuppression, such as in organ transplant recipients, further elevates the risk for aggressive forms like SCC and Merkel cell carcinoma.
The diagnostic approach to skin cancer begins with a thorough clinical evaluation, including a detailed history and full skin examination, often utilizing dermoscopy to enhance visualization of lesion architecture and pigment patterns. Suspicious lesions are assessed using the ABCDE criteria for melanoma (Asymmetry, Border irregularity, Color variation, Diameter >6 mm, Evolving characteristics) and analogous features for non-melanoma skin cancers. Definitive diagnosis requires histopathological confirmation, typically via excisional, incisional, or punch biopsy, with subsequent microscopic examination to determine tumor type, depth, and margin status. Immunohistochemistry may be employed for ambiguous cases or to differentiate between subtypes. Sentinel lymph node biopsy is indicated for select melanomas and Merkel cell carcinomas to assess regional nodal involvement. Imaging modalities, such as ultrasound, CT, MRI, or PET scans, are reserved for staging advanced disease or evaluating for metastasis. Molecular testing, including BRAF mutation analysis in melanoma, may guide targeted therapy decisions. Staging follows established criteria, such as the American Joint Committee on Cancer (AJCC) TNM system, to inform prognosis and management.
A range of pharmacological therapies are available for the treatment of skin cancer, each with distinct mechanisms of action and clinical indications. Lifileucel is an adoptive cell therapy utilizing autologous tumor-infiltrating lymphocytes, designed to enhance the immune-mediated destruction of cancer cells. Retifanlimab, a monoclonal antibody targeting PD-1, is employed to potentiate antitumor immune responses by inhibiting immune checkpoint pathways. Pucotenlimab, also acting as an immune checkpoint inhibitor, is administered to promote T-cell activity against malignant cells. The combination of nivolumab and relatlimab-rmbw leverages dual immune checkpoint blockade by targeting PD-1 and LAG-3, offering a synergistic approach to immunotherapy. Toripalimab is another PD-1 inhibitor used to restore immune surveillance and facilitate tumor regression. Cemiplimab, a fully human monoclonal antibody against PD-1, is indicated for certain advanced or metastatic skin cancers, providing durable responses in some patients. Encorafenib, a selective BRAF inhibitor, is prescribed for patients with BRAF-mutant melanoma, often in combination with other agents to inhibit downstream signaling pathways. Binimetinib, a MEK inhibitor, is frequently combined with BRAF inhibitors like encorafenib for enhanced efficacy in BRAF-mutant melanoma. Avelumab, an anti-PD-L1 monoclonal antibody, is utilized to disrupt the PD-1/PD-L1 interaction and reinvigorate antitumor immunity. Atezolizumab, also targeting PD-L1, is employed in the immunotherapeutic management of advanced skin malignancies, particularly in patients who are refractory to conventional treatments.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
| lifileucel (Rec INN; USAN) | 2306267-74-1 | |||
| retifanlimab (Rec INN; USAN); retifanlimab-dlwr | 2079108-44-2 | |||
| pucotenlimab (Prop INN; Rec INN) | 2403647-03-8 | |||
| nivolumab and relatlimab-rmbw; relatlimab/nivolumab | ||||
| toripalimab (Rec INN; USAN) | 1924598-82-2 | |||
| cemiplimab (Rec INN; USAN); cemiplimab-rwlc | 1801342-60-8 | |||
 | encorafenib (Rec INN; USAN) | 1269440-17-6 | C22 H27 Cl F N7 O4 S | 540.011 |
 | binimetinib (Rec INN; USAN) | 606143-89-9 | C17 H15 Br F2 N4 O3 | 441.227 |
| avelumab (Rec INN; USAN) | 1537032-82-8 | |||
| atezolizumab (Rec INN; USAN) | 1380723-44-3 |
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Skin Cancer
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