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Competing Interests: The authors report no conflicts of interest.

Epithelial membrane protein-2 (EMP2) is upregulated in a number of tumors and therefore remains a promising target for mAb-based therapy. In the current study, image-guided therapy for an anti-EMP2 mAb was evaluated by PET in both syngeneic and immunodeficient cancer models expressing different levels of EMP2 to enable a better understanding of its tumor uptake and off target accumulation and clearance. The therapeutic efficacy of the anti-EMP2 mAb was initially evaluated in high- and low-expressing tumors, and the mAb reduced tumor load for the high EMP2-expressing 4T1 and HEC-1-A tumors. To create an imaging agent, the anti-EMP2 mAb was conjugated to p-SCN-Bn-deferoxamine (DFO) and radiolabeled with 89Zr. Tumor targeting and tissue biodistribution were evaluated in syngeneic tumor models (4T1, CT26, and Panc02) and human tumor xenograft models (Ramos, HEC-1-A, and U87MG/EMP2). PET imaging revealed radioactive accumulation in EMP2-positive tumors within 24 hours after injection, and the signal was retained for 5 days. High specific uptake was observed in tumors with high EMP2 expression (4T1, CT26, HEC-1-A, and U87MG/EMP2), with less accumulation in tumors with low EMP2 expression (Panc02 and Ramos). Biodistribution at 5 days after injection revealed that the tumor uptake ranged from 2 to approximately 16%ID/cc. The results show that anti-EMP2 mAbs exhibit EMP2-dependent tumor uptake with low off-target accumulation in preclinical cancer models. The development of improved anti-EMP2 Ab fragments may be useful to track EMP2-positive tumors for subsequent therapeutic interventions., (©2024 American Association for Cancer Research.)

Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors.

Purpose: Research about academic medicine women faculty has focused on comparisons of men and women or specific groups who achieved leadership. To better understand the low percentages of women in academic medicine leadership, attention should be paid to the career continuum within genders. Study findings will inform policies and programs to support women in building careers and acquiring leadership positions. Materials and Methods: Association of American Medical Colleges (AAMC) StandPoint Faculty Engagement Survey data are used to describe and compare women assistant, associate and full professors' perceptions of (1) career development and advancement opportunities, and (2) a culture and climate that fosters diversity, equity, and inclusion. Specific similarities and differences with men are highlighted. Results: Fifty-nine percent of women respondents were assistant, 25% associate, and 16% full professors. Associate professors of both genders were the least satisfied on the main measures. Women were less satisfied than men at each career stage across the majority of variables. Among women, fewer than half of full and associate professors, and 52% of assistant professors believe they can express their opinions without fear of retribution. While the majority at all ranks (69%-75%) report feeling respected in the workplace, among those who did not, the highest percentage of disrespect based on gender was among associate professors. Conclusions: The perceptions of >7,500 academic medicine women faculty, representing different generations and ranks, underscore the need to broadly address gender inequity and sexism throughout the career continuum. It identifies the mid-career stage as a challenging experience for both men and women. Women, especially at the associate professor rank, remain a critically dissatisfied and underresourced group that is at risk for underutilization and potentially exit from academic medicine. All ranks of women need career development and equitable policies to support their sense of belonging and career advancement.