Divya B. Kenchappa

In the published publication [...].

Introduction: Acral lentiginous melanoma (ALM), a rare subtype, accounts for 2–3% of melanoma cases, primarily affecting the palms, soles, and nail beds and disproportionately affects people of color. This review focuses on clinical insights into ALM and its management, with a focus on race and ethnicity. Methods: A comprehensive literature search was conducted in public databases using the search term “acral melanoma,” and studies focusing on epidemiology, clinical presentation, and treatment outcomes of ALM in various racial and ethnic groups were reviewed. Results: Significant disparities in ALM outcomes exist across racial and ethnic groups, with African, Hispanic, and Asian individuals presenting with thicker, more advanced tumors at diagnosis. These populations encounter unique challenges, including limited access to dermatologic care, under-recognition of melanoma presentation in darker skin types, and socioeconomic barriers leading to delayed diagnosis and treatment. Surgical management may require specialized approaches, such as partial amputation for subungual melanomas. Additionally, there is uncertainty regarding the tumor immune microenvironment (TME) in ALM, with some studies suggesting that it might be less favorable, resulting in a lower response to immunotherapy. Conclusions: ALM affects diverse populations, and the impact of ethnic and racial origin on ALM biology is largely unknown. Addressing disparities in ALM outcomes among racial and ethnic groups is critical for improving patient care. Increased awareness of melanoma risk in individuals with darker skin can significantly impact early detection and treatment. Future research should focus on the genetic and biological factors contributing to morbidity and mortality in ALM patients.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.