Increased expression of musashi 1 on breast cancer cells has implication to understand dormancy and survival in bone marrow.

Breast cancer (BC) stem cells (CSCs) resist treatment and can exist as dormant cells in tissues such as the bone marrow (BM). Years before clinical diagnosis, BC cells (BCCs) could migrate from the primary site where the BM niche cells facilitate dedifferentiation into CSCs. Additionally, dedifferentiation could occur by cell autonomous methods. Here we studied the role of Msi 1, a RNA-binding protein, Musashi I (Msi 1). We also analyzed its relationship with the T-cell inhibitory molecule programmed death-ligand 1 (PD-L1) in CSCs. PD-L1 is an immune checkpoint that is a target in immune therapy for cancers. Msi 1 can support BCC growth through stabilization of oncogenic transcripts and modulation of stem cell-related gene expression. We reported on a role for Msi 1 to maintain CSCs. This seemed to occur by the differentiation of CSCs to more matured BCCs. This correlated with increased transition from cycling quiescence and reduced expression of stem cell-linked genes. CSCs co-expressed Msi 1 and PD-L1. Msi 1 knockdown led to a significant decrease in CSCs with undetectable PD-L1. This study has implications for Msi 1 as a therapeutic target, in combination with immune checkpoint inhibitor. Such treatment could also prevent dedifferentiation of breast cancer to CSCs, and to reverse tumor dormancy. The proposed combined treatment might be appropriate for other solid tumors.

Pilot Study Exploring the Feasibility of Incorporating Radiation Oncology Into Pre-existing Early Pathway Programs for Diverse Premedical Students.

PURPOSE: Many medical schools in the United States have affiliated pathway, preparatory, and/or prematriculation programs that enroll a high percentage of students historically underrepresented in medicine (URiM). The purpose of this pilot study was to better characterize exposures to radiation oncology (RO) among students in these programs and determine the feasibility of incorporating a radiation oncologist within their pre-existing format if nonexistent. METHODS AND MATERIALS: During the summers of 2021 and 2022, a radiation oncologist gave a presentation about basic principles of cancer care to 18 unique student groups in 12 premedical programs affiliated with 8 medical schools. Participating students were asked to complete an anonymous postpresentation questionnaire. Descriptive statistics are reported. RESULTS: A total of 467 students attended the presentations, and 241 completed the questionnaire (response rate 52.0%). The majority of participants reported being female (63.5%), URiM (66.4%), and low income (57.3%). Students were less likely to report previous teaching from a radiation oncologist (11.2%) than a surgical (17.0%) or medical oncologist (18.3%). Prior clinical shadowing with a radiation oncologist (2.9%) was also less likely than shadowing a surgical oncologist (5.0%), medical oncologist (6.6%), or any other physician (53.1%). Students were also less likely to previously believe that radiation could cure cancer (65.8%) compared with surgery (74.9%) or chemotherapy (89.3%). After the presentation, 168 students (69.7%) were more interested in a career in RO, and 211 students (87.6%) responded that the presentation was either quite or extremely valuable (median Likert-type score, 5; interquartile range, 4-5). CONCLUSIONS: Many of the students in premedical programs lack prior exposure to RO or knowledge of multidisciplinary cancer care, which was ameliorated by a simple yet effective presentation across a variety of different types of programs in this study. Longitudinal assessment of different types of educational initiatives and students' ultimate career trajectory will help optimize future RO initiatives among premedical URiM students.