Ionis Initiates Phase III Trial of Novel Antisense Medicine to Treat Leading Cause of Juvenile-Onset ALS

Ionis Pharmaceuticals, Inc. announced the initiation of a Phase III clinical trial of ION363 in patients with amyotrophic lateral sclerosis (ALS) with mutations in the fused in sarcoma gene.
[Ionis Pharmaceuticals, Inc.]
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Immune Stimulating Antibody‐Photosensitizer Conjugates via Fc‐Mediated Dendritic Cell Phagocytosis and Phototriggered Immunogenic Cell Death for KRAS‐Mutated Pancreatic Cancer Treatment

Cetuximab‐conjugated maleimide‐polyethylene glycol‐chlorin e6 (CMPC) was designed to strengthen its antitumor efficacy. With strong affinity for epidermal growth factor receptor overexpressing Aspc‐1 cells, CMPC with laser exerted the greatest cytotoxicity and induction of immunogenic cell death.
[Small]
Immune Stimulating Antibody‐Photosensitizer Conjugates via Fc‐Mediated Dendritic Cell Phagocytosis and Phototriggered Immunogenic Cell Death for KRAS‐Mutated Pancreatic Cancer Treatment - Kim - - Small - Wiley Online Library. (n.d.). Retrieved February 23, 2021, from https://onlinelibrary.wiley.com/doi/10.1002/smll.202006650 Cite
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Complement Activation Promoted by the Lectin Pathway Mediates C3aR-Dependent Sarcoma Progression and Immunosuppression

Scientists conducted a systematic assessment of the role of complement activation and effector pathways in sarcomas. Mice showed reduced susceptibility to 3-methylcholanthrene sarcomagenesis and transplanted sarcomas, whereas C1q and factor B deficiency had marginal effects.
[Nature Cancer]
Magrini, E., Di Marco, S., Mapelli, S. N., Perucchini, C., Pasqualini, F., Donato, A., Guevara Lopez, M. de la L., Carriero, R., Ponzetta, A., Colombo, P., Cananzi, F., Supino, D., Reis, E. S., Peano, C., Inforzato, A., Jaillon, S., Doni, A., Lambris, J. D., Mantovani, A., & Garlanda, C. (2021). Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression. Nature Cancer, 2(2), 218–232. https://doi.org/10.1038/s43018-021-00173-0 Cite
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Identification of Pannexin 1-Regulated Genes, Interactome, and Pathways in Rhabdomyosarcoma and Its Tumor Inhibitory Interaction with AHNAK

Scientists surveyed and characterized the molecular changes induced by PANX1 re-expression in rhabdomyosarcoma. They cataloged transcriptomic changes in this context by RNA sequencing.
[Oncogene]
Xiang, X., Langlois, S., St-Pierre, M.-E., Blinder, A., Charron, P., Graber, T. E., Fowler, S. L., Baird, S. D., Bennett, S. A. L., Alain, T., & Cowan, K. N. (2021). Identification of pannexin 1-regulated genes, interactome, and pathways in rhabdomyosarcoma and its tumor inhibitory interaction with AHNAK. Oncogene, 1–16. https://doi.org/10.1038/s41388-020-01623-2 Cite
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MNK1 and MNK2 Enforce Expression of E2F1, FOXM1, and WEE1 to Drive Soft Tissue Sarcoma

Researchers showed that depletion of either MAP kinase-interacting serine/threonine-protein kinase 1 or 2 (MNK1 or MNK2) suppressed cell viability, anchorage-independent growth, and tumorigenicity of soft tissue sarcoma cells.
[Oncogene]
Ke, X.-Y., Chen, Y., Tham, V. Y.-Y., Lin, R. Y.-T., Dakle, P., Nacro, K., Puhaindran, M. E., Houghton, P., Pang, A., Lee, V. K., Ding, L.-W., Gery, S., Hill, J., Chen, L., Xu, L., & Koeffler, H. P. (2021). MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma. Oncogene, 1–17. https://doi.org/10.1038/s41388-021-01661-4 Cite
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No Difference in Survival after HLA Mismatched versus HLA Matched Allogeneic Stem Cell Transplantation in Ewing Sarcoma Patients with Advanced Disease

Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, researchers analyzed 66 AES patients treated with allogeneic stem cell transplantation receiving HLA-mismatched versus HLA-matched grafts.
[Bone Marrow Transplantation]
Thiel, U., Schober, S. J., Ranft, A., Gassmann, H., Jabar, S., Gall, K., von Lüttichau, I., Wawer, A., Koscielniak, E., Diaz, M. A., Ussowicz, M., Kazantsev, I., Afanasyev, B., Merker, M., Klingebiel, T., Prete, A., Gruhn, B., Bader, P., Jürgens, H., … Lang, P. (2021). No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease. Bone Marrow Transplantation, 1–8. https://doi.org/10.1038/s41409-020-01200-x Cite
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Genome-Wide CRISPR-Cas9 Screen Identified KLF11 as a Druggable Suppressor for Sarcoma Cancer Stem Cells

Kruppel-like factor 11 (KLF11) recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop.
[Science Advances]
Wang, Y., Wu, J., Chen, H., Yang, Y., Xiao, C., Yi, X., Shi, C., Zhong, K., He, H., Li, Y., Wu, Z., Zhou, G., Rao, Q., Wang, X., Zhou, X., Lomberk, G., Liu, B., Zhao, J., Ge, J., … Qu, L. (2021). Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells. Science Advances, 7(5), eabe3445. https://doi.org/10.1126/sciadv.abe3445 Cite
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Opposing Immune and Genetic Mechanisms Shape Oncogenic Programs in Synovial Sarcoma

Synovial sarcoma (SyS) is an aggressive neoplasm driven by the SS18–SSX fusion, and is characterized by low T cell infiltration. Scientists studied the cancer-immune interplay in SyS using an integrative approach that combined single-cell RNA sequencing , spatial profiling and genetic and pharmacological perturbations.
[Nature Medicine]
Jerby-Arnon, L., Neftel, C., Shore, M. E., Weisman, H. R., Mathewson, N. D., McBride, M. J., Haas, B., Izar, B., Volorio, A., Boulay, G., Cironi, L., Richman, A. R., Broye, L. C., Gurski, J. M., Luo, C. C., Mylvaganam, R., Nguyen, L., Mei, S., Melms, J. C., … Regev, A. (2021). Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma. Nature Medicine, 1–12. https://doi.org/10.1038/s41591-020-01212-6 Cite
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Immunicum AB (publ) Receives FDA Orphan Drug Designation for Ilixadencel as a Treatment of Soft Tissue Sarcoma (STS)

Immunicum AB announced that it has received Orphan Drug Designation (ODD) from the FDA for the company’s lead candidate, ilixadencel, a cell-based, off-the-shelf immune primer, for the treatment of Soft Tissue Sarcoma.
[Immunicum AB]
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PI3K/Akt Pathway and Nanog Maintain Cancer Stem Cells in Sarcomas

Levels of Nanog and activated Akt were significantly higher in sarcoma cells grown as spheroids or sorted for CD133 expression to enrich for cancer stem cells.
[Oncogenesis]
Yoon, C., Lu, J., Yi, B. C., Chang, K. K., Simon, M. C., Ryeom, S., & Yoon, S. S. (2021). PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas. Oncogenesis, 10(1), 1–14. https://doi.org/10.1038/s41389-020-00300-z Cite
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Circulating Tumor DNA Is Detectable in Canine Histiocytic Sarcoma, Oral Malignant Melanoma, and Multicentric Lymphoma

Researchers used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. They detected circulating tumor DNA in 21/23 of histiocytic sarcoma, 2/8of oral melanoma, and 12/13 of lymphoma cases.
[Scientific Reports]
Prouteau, A., Denis, J. A., De Fornel, P., Cadieu, E., Derrien, T., Kergal, C., Botherel, N., Ulvé, R., Rault, M., Bouzidi, A., François, R., Dorso, L., Lespagnol, A., Devauchelle, P., Abadie, J., André, C., & Hédan, B. (2021). Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma. Scientific Reports, 11(1), 877. https://doi.org/10.1038/s41598-020-80332-y Cite
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