Exploiting Oxidative Phosphorylation to Promote the Stem and Immunoevasive Properties of Pancreatic Cancer Stem Cells

Investigators describe a 2D in vitro system for long-term enrichment of pancreatic cancer stem cells (CSCs) that was amenable to biological and CSC-specific studies.
[Nature Communications]
Valle, S., Alcalá, S., Martin-Hijano, L., Cabezas-Sáinz, P., Navarro, D., Muñoz, E. R., Yuste, L., Tiwary, K., Walter, K., Ruiz-Cañas, L., Alonso-Nocelo, M., Rubiolo, J. A., González-Arnay, E., Heeschen, C., Garcia-Bermejo, L., Hermann, P. C., Sánchez, L., Sancho, P., Fernández-Moreno, M. Á., & Sainz, B. (2020). Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells. Nature Communications, 11(1), 5265. https://doi.org/10.1038/s41467-020-18954-z Cite
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Pharmacological Ascorbate Inhibits Pancreatic Cancer Metastases via a Peroxide-Mediated Mechanism

Several in vitro and in vivo mechanisms involved in pancreatic cancer (PDAC) metastases were investigated following treatment with P-AscH. Serum from PDAC patients in clinical trials with P-AscH were tested for the presence and quantity of circulating tumor cell-derived nucleases.
[Scientific Reports]
O’Leary, B. R., Alexander, M. S., Du, J., Moose, D. L., Henry, M. D., & Cullen, J. J. (2020). Pharmacological ascorbate inhibits pancreatic cancer metastases via a peroxide-mediated mechanism. Scientific Reports, 10(1), 17649. https://doi.org/10.1038/s41598-020-74806-2 Cite
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Tenascin C Promotes Cancer Cell Plasticity in Mesenchymal Glioblastoma

Researchers identified Tenascin C (TNC) to be upregulated and secreted in mesenchymal glioblastoma subtype with high NF-κB signaling activity. Silencing TNC decreased proliferation, migration and suppresses self-renewal of glioma stem cells.
[Oncogene]
Angel, I., Pilo Kerman, O., Rousso-Noori, L., & Friedmann-Morvinski, D. (2020). Tenascin C promotes cancer cell plasticity in mesenchymal glioblastoma. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01506-6 Cite
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DYRK2 Controls a Key Regulatory Network in Chronic Myeloid Leukemia Stem Cells

Scientists discuss molecular maintenance in leukemia stem cells in chronic myeloid leukemia and provide a more in-depth discussion of the dual-specificity kinase DYRK2, which has been identified as a novel actionable checkpoint in a critical leukemic network.
[Experimental and Molecular Medicine]
Park, C. S., & Lacorazza, H. D. (2020). DYRK2 controls a key regulatory network in chronic myeloid leukemia stem cells. Experimental & Molecular Medicine, 1–10. https://doi.org/10.1038/s12276-020-00515-5 Cite
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FDA Approves Expanded Indication for Merck’s KEYTRUDA® (pembrolizumab) in Adult Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (cHL)

Merck announced that the FDA has approved an expanded label for KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma.
[Merck & Co., Inc.]
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Practical Classification of Triple-Negative Breast Cancer: Intratumoral Heterogeneity, Mechanisms of Drug Resistance, and Novel Therapies

Despite several efforts, transcriptomic and genomic classifications have remained merely theoretic and most of the patients are being treated with chemotherapy. Driver alterations in potentially targetable genes, including PIK3CA and AKT, have been identified across triple negative breast cancer subtypes, prompting the implementation of biomarker-driven therapeutic approaches.
[npj breast cancer]
Marra, A., Trapani, D., Viale, G., Criscitiello, C., & Curigliano, G. (2020). Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies. Npj Breast Cancer, 6(1), 1–16. https://doi.org/10.1038/s41523-020-00197-2 Cite
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Nanoparticle-Delivered Miriplatin Ultrasmall Dots Suppress Triple Negative Breast Cancer Lung Metastasis by Targeting Circulating Tumor Cells

Investigators found that active targeting nanoparticles displayed a superior DNA damage capability via enhanced-interactions with DNA and a significantly stronger effect in reducing cancer stem cell-like property of triple negative breast cancer cells, compared to conventional cisplatin and miriplatin.
[Journal of Controlled Release]
Li, Y., Qian, D., Lin, H.-P., Xie, J., Yang, P., Maddy, D., Xiao, Y., Huang, X., Wang, Z., & Yang, C. (2020). Nanoparticle-delivered miriplatin ultrasmall dots suppress triple negative breast cancer lung metastasis by targeting circulating tumor cells. Journal of Controlled Release. https://doi.org/10.1016/j.jconrel.2020.10.015 Cite
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RASSF1A Inhibits PDGFB-Driven Malignant Phenotypes of Nasopharyngeal Carcinoma Cells in a YAP1-Dependent Manner

The authors observed that ras-association domain family protein1 isoform A (RASSF1A) expression inhibited the malignant phenotypes of nasopharyngeal carcinoma (NPC) cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro.
[Cell Death & Disease]
Liang, Y.-Y., Deng, X.-B., Lin, X.-T., Jiang, L.-L., Huang, X.-T., Mo, Z.-W., Yuan, Y.-W., & Teh, M.-T. (2020). RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner. Cell Death & Disease, 11(10), 1–12. https://doi.org/10.1038/s41419-020-03054-z Cite
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WindMIL Therapeutics and Stephenson Cancer Center Announce Collaboration to Collect Bone Marrow from Patients with Renal and Urothelial Carcinomas to Develop Marrow Infiltrating Lymphocytes

WindMIL Therapeutics (WindMIL) and Stephenson Cancer Center announced that the first patients have been identified in an investigator-sponsored study for the collection of bone marrow from patients with renal and urothelial carcinomas. The study will evaluate generating marrow infiltrating lymphocytes for these patients through WindMIL’s proprietary cellular activation and expansion process.
[WindMIL Therapeutics (Globe Newswire, Inc.)]
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Transitional Dynamics of Cancer Stem Cells in Invasion and Metastasis

The authors advocate with substantial evidence the dynamic model of tumor propagation by exploring the specific cell types, reversible phenotypic plasticity between the tumorigenic leader seeds and the supporting follower cancer cells both in circulation and in solid tissue to accurately decipher tumor promoting clones and its role in metastatic dissemination and tumor re-growth.
[Translational Oncology]
Richard, V., Kumar, T. R. S., & Pillai, R. M. (2021). Transitional dynamics of cancer stem cells in invasion and metastasis. Translational Oncology, 14(1), 100909. https://doi.org/10.1016/j.tranon.2020.100909 Cite
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Jagged1-Notch1-Deployed Tumor Perivascular Niche Promotes Breast Cancer Stem Cell Phenotype through Zeb1

Scientists demonstrated that, with direct cell-cell contact, tumor microenvironment-derived endothelial cells provided the Notch ligand Jagged1 to neighboring breast cancer stem cells, leading to Notch1-dependent upregulation of Zeb1.
[Nature Communications]
Jiang, H., Zhou, C., Zhang, Z., Wang, Q., Wei, H., Shi, W., Li, J., Wang, Z., Ou, Y., Wang, W., Wang, H., Zhang, Q., Sun, W., Sun, P., & Yang, S. (2020). Jagged1-Notch1-deployed tumor perivascular niche promotes breast cancer stem cell phenotype through Zeb1. Nature Communications, 11(1), 5129. https://doi.org/10.1038/s41467-020-18860-4 Cite
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