Browsing by Subject "Skin Neoplasms"
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Item Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma(2016-06-23) Eskiocak, Banu; DeBerardinis, Ralph J.; White, Michael A.; Brekken, Rolf A.; Cobb, Melanie H.Genomic diversity and adaptive plasticity of melanoma tumors limit durable control with conventional and targeted therapies. Nevertheless, pathological activation of the ERK1/2 regulatory system is a linchpin tumorigenic mechanism associated with the majority of both primary and recurrent disease. To avoid common resistance mechanisms associated with perdurance of ERK1/2 signaling, we sought to identify therapeutic targets that are selectively required for tumorigenicity in the presence of pathological ERK1/2 signaling. Such targets could be leveraged in jiu jitsu fashion to breach selective pressure to engage any of the many BRAF-independent ERK1/2 pathway activation mechanisms. By integration of multi-genome chemical and genetic screens; recurrent architectural variants in melanoma tumor genomes; and patient outcome data; we identified 2 mechanistic subtypes of BRAF(V600) melanoma that inform new cancer cell biology and offer new therapeutic opportunities. Subtype membership defines sensitivity to clinical MEK inhibitors versus TBK1/IKBKE inhibitors. Importantly, subtype membership can be predicted using a robust quantitative 5-feature genetic biomarker. This biomarker, or the mechanistic relationships linked to it, can identify a cohort of best responders to clinical MEK inhibitors (detectable in 25% of melanoma patients) and identify a cohort of TBK1/IKBKE inhibitor-sensitive disease among non-responders to current targeted therapy (detectable in 9.9% of melanomas).Item Clinical Features and Outcomes of Black Patients with Melanoma: A Case Series Between 2006-2022(2024-01-30) Brown, Ariel B.; Wix, Sophia N.; Heberton, Meghan; Adamson, Adewole S.; Gill, Jennifer G.BACKGROUND: The incidence of melanoma in Black patients is rare, therefore most studies describing outcomes have been performed using population databases with limited patient-level information. OBJECTIVE: To describe specific anatomic sites, clinical features, histologic subtypes, risk factors, and outcomes of Black patients with melanoma. METHODS: Case series of Black patients with melanoma identified between January 2006 and October 2022 at University of Texas Southwestern Medical Center and Parkland Health in Dallas, TX. Participants included self-identified Black patients with a histopathologic diagnosis of melanoma. Data collection included demographics, clinical characteristics, personal and family medical history, immunosuppression history, comorbidities, histopathology reports, imaging reports, melanoma treatments and responses, time to progression, metastatic sites, and survival. Kaplan-Meier analysis captured melanoma-related survival by primary site. RESULTS: Of the 48 patients identified, the median age at diagnosis of melanoma was 61.5 (range: 23-86) with the majority being female (30/48). Seventy-five percent (30/40) of primary cutaneous melanomas were located on acral skin despite only one-third (10/30) being histologically classified as acral lentiginous melanomas. Compared to those with acral disease, patients with non-acral cutaneous melanomas were more likely to be immunocompromised (40% vs. 7%) or have a personal history of cancer (60% vs. 17%) with all (3/3) superficial spreading melanoma patients having a history of both. No patients had more than 1 confirmed primary melanoma. In total, 13 (27%) Black patients with melanoma developed stage IV disease, of which 12 ultimately died due to disease progression. Those diagnosed with advanced acral melanoma, mucosal/ocular melanoma, or unknown primary had the poorest melanoma outcomes. No patients with non- acral cutaneous melanomas developed distant metastases or died of their disease. CONCLUSION: Most cutaneous melanomas in Black patients occur on acral sites. Non-acral cutaneous melanomas had limited contribution to melanoma mortality in Black patients and were diagnosed primarily in immunocompromised patients or those with a history of other cancers. Improving melanoma mortality in Black patients will require focused therapeutic and early detection strategies for acral, mucosal/ocular, and melanoma of unknown primary.Item [News](1979-08-14) Rutherford, SusanItem [Southwestern News](2004-12-10) Satyanarayana, MeghaItem [Southwestern News](1993-03-31) Swendson, ShannaItem Sunlight and skin cancer(1981-04-23) Bergstresser, Paul R.Item [UT News](1987-04-29) Rutherford, SusanItem [UT Southwestern Medical Center News](2012-11-07) Carlton, JeffreyItem [UT Southwestern Medical Center News](2009-08-10) Rian, Russell