Breast cancer brain metastases (BCBM) are a significant cause of mortality and are incurable. Thus, identifying BCBM targets that reduce morbidity and mortality is critical. BCBM upregulate Stearoyl-CoA Desaturase (SCD), an enzyme that catalyzes the synthesis of monounsaturated fatty acids, suggesting a potential metabolic vulnerability of BCBM. In this study, we tested the effect of a brain-penetrant clinical-stage inhibitor of SCD (SCDi), on breast cancer cells and mouse models of BCBM. Lipidomics, qPCR, and western blot were used to study the in vitro effects of SCDi. Single-cell RNA sequencing was used to explore the effects of SCDi on cancer and immune cells in a BCBM mouse model. Pharmacological inhibition of SCD markedly reshaped the lipidome of breast cancer cells and resulted in endoplasmic reticulum stress, DNA damage, loss of DNA damage repair, and cytotoxicity. Importantly, SCDi alone or combined with a PARP inhibitor prolonged the survival of BCBM-bearing mice. When tested in a syngeneic mouse model of BCBM, scRNAseq revealed that pharmacological inhibition of SCD enhanced antigen presentation by dendritic cells, was associated with a higher interferon signaling, increased the infiltration of cytotoxic T cells, and decreased the proportion of exhausted T cells and regulatory T cells in the tumor microenvironment (TME). Additionally, pharmacological inhibition of SCD decreased engagement of immunosuppressive pathways, including the PD-1:PD-L1/PD-L2 and PVR/TIGIT axes. These findings suggest that SCD inhibition could be an effective strategy to intrinsically reduce tumor growth and reprogram anti-tumor immunity in the brain microenvironment to treat BCBM.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100738 | PMC |
http://dx.doi.org/10.1101/2024.05.06.592766 | DOI Listing |
Breast Cancer Res
January 2025
Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road, Hangzhou, Zhejiang, China.
Background: Neoadjuvant chemotherapy (NACT) is the standard-of-care treatment for patients with locally advanced breast cancer (LABC), providing crucial benefits in tumor downstaging. Clinical parameters, such as molecular subtypes, influence the therapeutic impact of NACT. Moreover, severe adverse events delay the treatment process and reduce the effectiveness of therapy.
View Article and Find Full Text PDFBMC Cancer
January 2025
Division of Clinical Research and Technological Development, Brazilian National Cancer Institute, 37 Andre Cavalcanti Street, 5th floor, Annex Building, 20231050, Rio de Janeiro, Brazil.
Background: Breast cancer (BC) has exhibited varied epidemiological trends based on distinct age categories. This research aimed to explore the incidence and mortality rates of BC within pre-defined age groups in the Brazilian population.
Methods: BC incidence trends were assessed from 2010 to 2015 using Brazilian Population-Based Cancer Registries, employing age-standardized ratios and annual average percentage change (AAPC).
BMC Med Imaging
January 2025
Electronics and Communications, Arab Academy for Science, Heliopolis, Cairo, 2033, Egypt.
Invasive breast cancer diagnosis and treatment planning require an accurate assessment of human epidermal growth factor receptor 2 (HER2) expression levels. While immunohistochemical techniques (IHC) are the gold standard for HER2 evaluation, their implementation can be resource-intensive and costly. To reduce these obstacles and expedite the procedure, we present an efficient deep-learning model that generates high-quality IHC-stained images directly from Hematoxylin and Eosin (H&E) stained images.
View Article and Find Full Text PDFMed Phys
January 2025
Department of Scientific Research and Academic, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, P. R. China.
Background: This study aims to explore the value of habitat-based magnetic resonance imaging (MRI) radiomics for predicting the origin of brain metastasis (BM).
Purpose: To investigate whether habitat-based radiomics can identify the metastatic tumor type of BM and whether an imaging-based model that integrates the volume of peritumoral edema (VPE) can enhance predictive performance.
Methods: A primary cohort was developed with 384 patients from two centers, which comprises 734 BM lesions.
Breast Cancer Res Treat
January 2025
University of Pittsburgh School of Medicine (Center for Clinical Genetics and Genomics), Pittsburgh, PA, USA.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!