Melanoma
Skin cancer is the most commonly diagnosed cancer in the United States.1 Invasive melanoma accounts for approximately 1% of skin cancer diagnoses but has the highest mortality of all skin cancer cases.1 Cutaneous melanomas comprise ~90% of all diagnosed melanoma cases.2 Melanoma pathogenesis may be described according to its molecular characterization.
MAPK. The mitogen-activated protein kinase (MAPK) pathway is aberrantly activated in over 80% of primary melanomas, with mutations along this pathway (RAS-RAF-MEK-ERK) being mutually exclusive.3
BRAF. BRAF-mutant melanomas occur in up to 50% of melanoma cases. They tend to occur in younger patients, appear on the trunk or limbs, and are associated with low cumulative solar damage.3
NRAS. Approximately 15% to 20% of patients with melanoma present with NRAS mutations. These mutations are typically associated with low or absent pagetoid epidermal scatter and peripheral circumscription.3
Incidence in the United States
It was estimated that in 2023, 97,610 new cases of invasive melanoma would be diagnosed in the United States.1 Melanoma comprises 5% of all new cancer cases.4 Among patients <50 years old, incidence rates are higher in women than in men; however, among patients >50 years old, incidence rates are higher in men than in women.1 This shift is due to differences in historic occupational and recreational exposure to ultraviolet radiation, including the use of indoor tanning.1 However, in adults >50 years old, incidence rates increased by ~1% annually for women but stabilized for men from 2015 to 2019.1 It was projected that in 2023, an estimated 7990 deaths would be due to melanoma.1
Epidemiology in the United States
Most patients (82%) present with localized melanoma.4 Such patients exhibit a 5-year survival rate of 99.5%.4 Survival rates decrease, however, among those with regional (9%) or distant (4%) metastasis, with 5-year survival reported to be 71% and 32%, respectively.4
Risk Factors
Melanoma is associated with both modifiable and nonmodifiable risk factors.2 Modifiable risk factors include indoor tanning, ultraviolet exposure, and medications.2 Nonmodifiable factors that may contribute to melanoma risk include genetics, family history, socioeconomic status, nevi, race, age, and sex.2
Unmet Need
Though melanoma may be rare, accounting for 1% of all skin cancers, metastatic melanoma has a 5-year survival rate of only 30%.1,4 Furthermore, cutaneous melanoma has the highest mortality rate of all skin cancers, indicating an unmet need among this patient population.1
References: 1. American Cancer Society. Cancer Facts and Figures 2023. 2. Carr et al. Surg Clin North Am. 2020;100:1-12. 3. Scolyer et al. Mol Oncol. 2011;5:124-136. 4. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Melanoma of the Skin. https://seer.cancer.gov/statfacts/html/melan.html. Accessed September 1, 2022.
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