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Breast cancer is the second leading cause of death in women globally, and it remains a health burden due to poor therapy response, cancer cell drug resistance, and the debilitating side effects associated with most therapies. One approach to addressing the need to improve breast cancer therapies has been to elucidate the mechanism(s) underpinning this disease to identify key drivers that can be targeted in molecular therapies. The T-box transcription factor, TBX3, is upregulated in breast cancer, in which it contributes to important oncogenic processes, and it has been validated as a potential therapeutic target. Here, we investigated the molecular mechanisms that upregulate TBX3 in breast cancer, and we show that it involves transcriptional activation by c-Myc, post-translational modification by AKT1 and AKT3, and interaction with the molecular chaperone Hsc70. Together, the results from this study provide evidence that c-Myc, AKT, Hsc70, and TBX3 form part of an important oncogenic pathway in breast cancer and thus reveal versatile ways of interfering with the oncogenic activity of TBX3 for the treatment of this neoplasm. Implications: Targeting the c-Myc/AKT/TBX3/Hsc70 signaling axis may be an effective treatment strategy for TBX3-driven breast cancer., (©2024 American Association for Cancer Research.)

Introduction: The overdose crisis in the U.S. disproportionately impacts people experiencing homelessness. Permanent supportive housing (PSH) - permanent, affordable housing with voluntary support services - is an effective, evidence-based intervention to address homelessness. However, overdose risk remains high even after entering PSH for individual and structural reasons. In this study, we aimed to refine a set of evidence-based overdose prevention practices (EBPs) and an associated implementation support package for PSH settings using focus groups with PSH tenants, frontline staff, and leaders., Methods: Our community-academic team identified an initial set of overdose EBPs applicable for PSH through research, public health guidance, and a needs assessment. We adapted these practices based on feedback from focus groups with PSH leaders, staff, and tenants. Focus groups followed semi-structured interview guides developed using the EPIS (Exploration, Preparation, Implementation, Sustainment) framework constructs of inner context, outer context, and bridging factors related to overdose prevention and response., Results: We conducted 16 focus groups with 40 unique participants (14 PSH tenants, 15 PSH staff, 11 PSH leaders); focus groups were held in two iterative rounds and individuals could participate in one or both rounds. Participants were diverse in gender, race, and ethnicity. Focus group participants were enthusiastic about the proposed EBPs and implementation strategies, while contributing unique insights and concrete suggestions to improve upon them. The implementation support package contains an iteratively refined PSH Overdose Prevention (POP) Toolkit with 20 EBPs surrounding overdose prevention and response, harm reduction, and support for substance use treatment and additional core implementation strategies including practice facilitation, tenant-staff champion teams, and learning collaboratives., Conclusions: This manuscript describes how robust community-academic partnerships and input from people with lived experience as tenants and staff in PSH informed adaptation of evidence-based overdose prevention approaches and implementation strategies to improve their fit for PSH settings. This effort can inform similar efforts nationally in other settings serving highly marginalized populations. We are currently conducting a randomized trial of the refined overdose prevention implementation support package in PSH., Competing Interests: Declaration of competing interest The authors do not report any competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)