SHP2 Is a Multifunctional Therapeutic Target in Drug Resistant Metastatic Breast Cancer

Scientists used inducible genetic depletion and two distinct pharmacological inhibitors to investigate the therapeutic potential of targeting SH2 containing protein tyrosine phosphatase-2 (SHP2) in metastatic breast cancer.
[Oncogene]
Chen, H., Libring, S., Ruddraraju, K. V., Miao, J., Solorio, L., Zhang, Z.-Y., & Wendt, M. K. (2020). SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01488-5 Cite
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Immune Remodeling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection

Extracellular matrix-rich tumors exhibited a stem cell-like gene expression profile and superior tumor-initiating capacity, whereas such features were absent in responder tumors.
[Cancer Immunology Research]
Pires, A., Greenshields-Watson, A., Jones, E., Smart, K., Lauder, S. N., Somerville, M., Milutinovic, S., Kendrick, H., Hindley, J. P., French, R., Smalley, M. J., Watkins, W. J., Andrews, R., Godkin, A., & Gallimore, A. (2020). Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0070 Cite
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Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection

Scientists defined an extended role for an effective immune response, not just in direct killing of tumor cells, but in widescale remodelling of the tumor microenvironment to favor loss of ECM, elimination of cancer stem cells, and propagation of adaptive immunity.
[Cancer Immunology Research]
Pires, A., Greenshields-Watson, A., Jones, E., Smart, K., Lauder, S. N., Somerville, M., Milutinovic, S., Kendrick, H., Hindley, J. P., French, R., Smalley, M. J., Watkins, W. J., Andrews, R., Godkin, A., & Gallimore, A. (2020). Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0070 Cite
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Oncolytic Reovirus-Mediated Recruitment of Early Innate Immune Response Reverses Immunotherapy-Resistance in Prostate Tumors by Inducing a T-Cell Inflamed Microenvironment

Oncolytic virus therapy can potentially overcome resistance to immunotherapy in prostate cancers by transforming cold tumors into ‘hot’, immune cell-infiltrated tumors. Scientists investigated whether the combination of intratumoural oncolytic reovirus, followed by targeted blockade of PD-1 checkpoint inhibition and/or the immunomodulatory CD73/Adenosine system could enhance anti-tumor immunity.
[Molecular Therapy-Oncolytics]
Annels, N. E., Simpson, G. R., Denyer, M., Arif, M., Coffey, M., Melcher, A., Harrington, K., Vile, R., & Pandha, H. (2020). Oncolytic reovirus-mediated recruitment of early innate immune response reverses immunotherapy-resistance in prostate tumours by inducing a T-cell inflamed microenvironment. Molecular Therapy - Oncolytics, 0(0). https://doi.org/10.1016/j.omto.2020.09.010 Cite
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Exosomal Long Non-Coding RNAs: Emerging Players in the Tumor Microenvironment

The present review article discusses the role of exosomal lncRNAs in the crosstalk between tumor cells and the surrounding cells of the microenvironment.
[Molecular Therapy-Nucleic Acids]
Pathania, A. S., & Challagundla, K. B. (2020). Exosomal long non-coding RNAs: Emerging players in the tumor microenvironment. Molecular Therapy - Nucleic Acids, 0(0). https://doi.org/10.1016/j.omtn.2020.09.039 Cite
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TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment

Scientists identified a constitutive mechanism of resistance to PARP inhibitor (PARPi). They report that the bone marrow microenvironment facilitates DNA double-strand break repair activity in leukemia cells to protect them against PARPi-mediated synthetic lethality.
[Cell Reports]
Le, B. V., Podszywalow-Bartnicka, P., Maifrede, S., Sullivan-Reed, K., Nieborowska-Skorska, M., Golovine, K., Yao, J.-C., Nejati, R., Cai, K. Q., Caruso, L. B., Swatler, J., Dabrowski, M., Lian, Z., Valent, P., Paietta, E. M., Levine, R. L., Fernandez, H. F., Tallman, M. S., Litzow, M. R., … Skorski, T. (2020). TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment. Cell Reports, 33(1). https://doi.org/10.1016/j.celrep.2020.108221 Cite
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Arch Oncology Advances Anti-CD47 Antibody AO-176 into Chemotherapy Combination Phase I-II Trial in Solid Tumors

Arch Oncology, Inc. has announced the expansion of AO-176’s clinical development into a Phase I/II chemotherapy combination trial for patients with select solid tumors. AO-176 is an anti-CD47 antibody with a potential best-in-class profile that works by blocking the “don’t eat me” signal and also by preferentially binding to tumor cells in their acidic microenvironment.
[Arch Oncology, Inc.]
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Codiak Initiates Patient Dosing in Phase I/II Clinical Trial of exoSTING™ for the Treatment of Solid Tumors

Codiak BioSciences, Inc.,has announced the initiation of patient dosing in its Phase I/II clinical trial of exoSTING, a novel exosome therapeutic candidate engineered with the company’s engEx Platform and designed to deliver Codiak’s proprietary STING agonist specifically to tumor-resident antigen presenting cells in the tumor microenvironment.
[Codiak BioSciences, Inc.]
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The Role of Integrins in Inflammation and Angiogenesis

This review presents current evidence from human and animal studies on integrin structure and molecular signaling, with particular emphasis on signal transduction in infants.
[Pediatric Research]
Mezu-Ndubuisi, O. J., & Maheshwari, A. (2020). The role of integrins in inflammation and angiogenesis. Pediatric Research, 1–9. https://doi.org/10.1038/s41390-020-01177-9 Cite
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Inhibition of eNOS by L-NAME Resulting in Rat Hind Limb Developmental Defects through PFKFB3 Mediated Angiogenetic Pathway

In vivo studies showed that NOS inhibition strongly suppressed hind limb angiogenetic remodeling by impairing differentiation of endothelial cells and smooth muscle cells, and extracellular matrix synthesis.
[Scientific Reports]
Wu, Z., Yao, H., Xu, H., Wang, Y., Hu, W., Lou, G., Zhang, L., Huang, C., Jiang, C., Zhou, S., Shi, Y., Chen, X., Yang, L., Xu, Y., & Wang, Y. (2020). Inhibition of eNOS by L-NAME resulting in rat hind limb developmental defects through PFKFB3 mediated angiogenetic pathway. Scientific Reports, 10(1), 16754. https://doi.org/10.1038/s41598-020-74011-1 Cite
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In Situ-Forming Collagen Hydrogel Crosslinked via Multi-Functional Peg as a Matrix Therapy for Corneal Defects

The authors report on the development of an in situ-forming hydrogel of collagen type I crosslinked via multi-functional polyethylene glycol (PEG)-N-hydroxysuccinimide and characterize its biophysical properties and regenerative capacity both in vitro and in vivo.
[Scientific Reports]
Fernandes-Cunha, G. M., Chen, K. M., Chen, F., Le, P., Han, J. H., Mahajan, L. A., Lee, H. J., Na, K. S., & Myung, D. (2020). In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects. Scientific Reports, 10(1), 16671. https://doi.org/10.1038/s41598-020-72978-5 Cite
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