From Desegregation and Integration to Diversity and Inclusion: The Environment Was Just Ice.

The process of desegregation at Southern schools of pharmacy was long and arduous. Despite persistent protests, struggles, and lawsuits, many schools of pharmacy did not graduate their first Black students until the 1970s. The School of Pharmacy at the University of North Carolina at Chapel Hill unintentionally desegregated in 1962 when its first Black student, William Wicker, was inadvertently admitted. His personal story and those of his fellow pioneers in desegregation, Mona (Boston) Reddick and James Barnes, provide valuable context to Diversity, Equity, and Inclusion efforts. The historical proximity of desegregation affords the pharmacy profession only one or two generations of Black pharmacists trained during an era when Southern pharmacy education was broadly available. These stories personify the legacy of segregation, confront the ongoing impact of structural racism, and meaningfully inform conversations about Diversity, Equity, and Inclusion in pharmacy education.

Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma.

PURPOSE: Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need.Experimental Design: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo. RESULTS: ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib. CONCLUSIONS: These data support a "first in RDEB" phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC.