A High-Dimensional Window into the Micro-Environment of Triple Negative Breast Cancer

Investigators discuss the cellular phenotypes and spatial patterns of the lymphoid-, myeloid-, and stromal cells in the TNBC microenvironment and the potential value of mapping these features onto tumor cell genotypes.
[Cancers]
Nederlof, I., Horlings, H. M., Curtis, C., & Kok, M. (2021). A High-Dimensional Window into the Micro-Environment of Triple Negative Breast Cancer. Cancers, 13(2), 316. https://doi.org/10.3390/cancers13020316 Cite
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Multiple Screening Approaches Reveal HDAC6 as a Novel Regulator of Glycolytic Metabolism in Triple-Negative Breast Cancer

Investigators set up a phenotypic small-molecule screen to reveal vulnerabilities in TNBC cells that were independent of mitochondrial apoptosis. Using a functional genetic approach, they identified that a “hit” compound, BAS-2, had a potentially similar mechanism of action to histone deacetylase inhibitors.
[Science Advances]
Dowling, C. M., Hollinshead, K. E. R., Grande, A. D., Pritchard, J., Zhang, H., Dillon, E. T., Haley, K., Papadopoulos, E., Mehta, A. K., Bleach, R., Lindner, A. U., Mooney, B., Düssmann, H., O’Connor, D., Prehn, J. H. M., Wynne, K., Hemann, M., Bradner, J. E., Kimmelman, A. C., … Chonghaile, T. N. (2021). Multiple screening approaches reveal HDAC6 as a novel regulator of glycolytic metabolism in triple-negative breast cancer. Science Advances, 7(3), eabc4897. https://doi.org/10.1126/sciadv.abc4897 Cite
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Spliceosome-Targeted Therapies Trigger an Antiviral Immune Response in Triple-Negative Breast Cancer

Scientists discovered that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven TNBC, spliceosome-targeted therapies caused widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures.
[Cell]
Bowling, E. A., Wang, J. H., Gong, F., Wu, W., Neill, N. J., Kim, I. S., Tyagi, S., Orellana, M., Kurley, S. J., Dominguez-Vidaña, R., Chung, H.-C., Hsu, T. Y.-T., Dubrulle, J., Saltzman, A. B., Li, H., Meena, J. K., Canlas, G. M., Chamakuri, S., Singh, S., … Westbrook, T. F. (2021). Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer. Cell, 0(0). https://doi.org/10.1016/j.cell.2020.12.031 Cite
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Novel Iodine Nanoparticles Target Vascular Mimicry in Intracerebral Triple Negative Human MDA-MB-231 Breast Tumors

MDA-MB-231-cells, iodine nanoparticles, and CD31 were examined by fluorescence confocal microscopy.
[Scientific Reports]
Ridwan, S. M., Hainfeld, J. F., Ross, V., Stanishevskiy, Y., & Smilowitz, H. M. (2021). Novel Iodine nanoparticles target vascular mimicry in intracerebral triple negative human MDA-MB-231 breast tumors. Scientific Reports, 11(1), 1203. https://doi.org/10.1038/s41598-020-80862-5 Cite
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Polysaccharide Hydrogel Based 3D Printed Tumor Models for Chemotherapeutic Drug Screening

Results of flow property, shape fidelity, scaffold stability and biocompatibility of H4-RGD suggest that the proposed hydrogel could be considered for 3D cell bioprinting and also for in vitro tumor microenvironment development for high throughput screening of various anti-cancer drugs.
[Scientific Reports]
Gebeyehu, A., Surapaneni, S. K., Huang, J., Mondal, A., Wang, V. Z., Haruna, N. F., Bagde, A., Arthur, P., Kutlehria, S., Patel, N., Rishi, A. K., & Singh, M. (2021). Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening. Scientific Reports, 11(1), 372. https://doi.org/10.1038/s41598-020-79325-8 Cite
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Everest Medicines Initiates Submission of New Drug Application in Singapore for Sacituzumab Govitecan-Hziy for the Treatment of Metastatic Triple-Negative Breast Cancer

Everest Medicines announced that it has initiated the submission of a New Drug Application to the Health Sciences Authority of Singapore for sacituzumab govitecan-hziy for the treatment of patients with metastatic TNBC who have received at least two prior therapies for metastatic disease.
[Everest Medicines]
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BTF3 Promotes Stemness and Inhibits Type Ⅰ Interferon Signaling Pathway in Triple-Negative Breast Cancer

Researchers demonstrated that BTF3 expression is related with stem-like properties in triple negative breast cancer (TNBC) cells. BTF3 modulated stemness, migration and proliferation of TNBC in vitro.
[Biochemical and Biophysical Research Communications]
Wang, H., Gao, L., Qi, M., Su, P., Xiong, X., Zhao, J., Hu, J., & Han, B. (2021). BTF3 promotes stemness and inhibits TypeⅠInterferon signaling pathway in triple-negative breast cancer. Biochemical and Biophysical Research Communications, 537, 22–28. https://doi.org/10.1016/j.bbrc.2020.12.060 Cite
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HES1 Promotes Breast Cancer Stem Cells by Elevating Slug in Triple-Negative Breast Cancer

Investigators revealed that HES1 is a novel transcriptional activator for Slug through acting directly on its promoter. HES1 knockdown reduced breast cancer stem cell (BCSC) self-renewal, BCSC population, and cancer cell proliferation in TNBC, whereas overexpression of Slug restored the oncogenic function of HES1, both in vitro and in vivo.
[International Journal of Biological Sciences]
Li, X., Li, Y., Du, X., Wang, X., Guan, S., Cao, Y., Jin, F., & Li, F. (2021). HES1 promotes breast cancer stem cells by elevating Slug in triple-negative breast cancer. International Journal of Biological Sciences, 17(1), 247–258. https://doi.org/10.7150/ijbs.53477 Cite
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Integrin αvβ6–TGFβ–SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer

The authors identified the SOX4 transcription factor as an important resistance mechanism to T cell-mediated cytotoxicity for TNBC cells
[Cancer Cell]
Bagati, A., Kumar, S., Jiang, P., Pyrdol, J., Zou, A. E., Godicelj, A., Mathewson, N. D., Cartwright, A. N. R., Cejas, P., Brown, M., Giobbie-Hurder, A., Dillon, D., Agudo, J., Mittendorf, E. A., Liu, X. S., & Wucherpfennig, K. W. (2020). Integrin αvβ6–TGFβ–SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2020.12.001 Cite
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YY1-Mediated Long Non-Coding RNA Kcnq1ot1 Promotes the Tumor Progression by Regulating PTEN via DNMT1 in Triple Negative Breast Cancer

The authors identified the roles of YY1-mediated long non-coding RNA Kcnq1ot1 in TNBC.
[Cancer Gene Therapy]
Shen, B., Li, Y., Ye, Q., & Qin, Y. (2020). YY1-mediated long non-coding RNA Kcnq1ot1 promotes the tumor progression by regulating PTEN via DNMT1 in triple negative breast cancer. Cancer Gene Therapy, 1–14. https://doi.org/10.1038/s41417-020-00254-9 Cite
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Selective Glutamine Metabolism Inhibition in Tumor Cells Improves Anti-Tumor T Lymphocyte Activity in Triple-Negative Breast Cancer

Investigators report an inverse correlation between glutamine metabolic genes and markers of T cell-mediated cytotoxicity in human basal-like breast cancer patient datasets, with increased glutamine metabolism and decreased T cell cytotoxicity associated with poor survival.
[Journal of Clinical Investigation]
Edwards, D. N., Ngwa, V. M., Raybuck, A. L., Wang, S., Hwang, Y., Kim, L. C., Cho, S. H., Paik, Y., Wang, Q., Zhang, S., Manning, H. C., Rathmell, J. C., Cook, R. S., Boothby, M. R., & Chen, J. (2020). Selective glutamine metabolism inhibition in tumor cells improves anti-tumor T lymphocyte activity in triple-negative breast cancer. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI140100 Cite
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