Dopamine Improves Chemotherapeutic Efficacy for Pancreatic Cancer by Regulating Macrophage-Derived Inflammations

The roles and mechanisms of dopamine to affect the chemotherapeutic efficacy for pancreatic cancer were studied. Multi-omics results revealed that there was a tumor-promoting vicious cycle involving murine pancreatic cancer cells and tumor-associated macrophages.
[Cancer Immunology Immunotherapy]
Liu, Q., Zhang, R., Zhang, X., Liu, J., Wu, H., Li, Y., Cui, M., Li, T., Song, H., Gao, J., Zhang, Y., Yang, S., & Liao, Q. (2021). Dopamine improves chemotherapeutic efficacy for pancreatic cancer by regulating macrophage-derived inflammations. Cancer Immunology, Immunotherapy. https://doi.org/10.1007/s00262-020-02816-0 Cite
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ATDC Binds to KEAP1 to Drive NRF2-Mediated Tumorigenesis and Chemoresistance in Pancreatic Cancer

Researchers revealed that increased ataxia-telangiectasia group D-associated gene (ATDC) levels protected cancer cells from reactive oxygen species via stabilization of nuclear factor erythroid 2-related factor 2 (NRF2).
[Genes & Development]
Purohit, V., Wang, L., Yang, H., Li, J., Ney, G. M., Gumkowski, E. R., Vaidya, A. J., Wang, A., Bhardwaj, A., Zhao, E., Dolgalev, I., Zamperone, A., Abel, E. V., Magliano, M. P. D., Crawford, H. C., Diolaiti, D., Papagiannakopoulos, T. Y., Lyssiotis, C. A., & Simeone, D. M. (2021). ATDC binds to KEAP1 to drive NRF2-mediated tumorigenesis and chemoresistance in pancreatic cancer. Genes & Development. https://doi.org/10.1101/gad.344184.120 Cite
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Combining NanoKnife with M1 Oncolytic Virus Enhances Anticancer Activity in Pancreatic Cancer

Scientists evaluated improvements to therapeutic efficacy through combination therapy incorporating NanoKnife and M1 virus. They showed that irreversible electroporation triggered reactive oxygen species-dependent apoptosis in pancreatic cancer cells mediated by phosphatidylinositol-3-kinase/protein kinase B pathway suppression.
[Cancer Letters]
Sun, S., Liu, Y., He, C., Hu, W., Liu, W., Huang, X., Wu, J., Xie, F., Chen, C., Wang, J., Lin, Y., Zhu, W., Yan, G., Cai, J., & Li, S. (2021). Combining NanoKnife with M1 oncolytic virus enhances anticancer activity in pancreatic cancer. Cancer Letters, 502, 9–24. https://doi.org/10.1016/j.canlet.2020.12.018 Cite
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A MET Targeting Antibody-Drug Conjugate Overcomes Gemcitabine Resistance in Pancreatic Cancer

Scientists evaluated the efficacy of TR1801-ADC, a newly developed ADC composed of a MET antibody conjugated to the highly potent pyrrolobenzodiazepine toxin-linker Tesirine. They first evaluated MET expression and subcellular localization in pancreatic cancer cell lines, human tumors and patient derived xenografts.
[Clinical Cancer Research]
Cazes, A., Betancourt, O., Esparza, E., Mose, E. S., Jaquish, D., Wong, E., Wascher, A. A., Tiriac, H., Gymnopoulos, M., & Lowy, A. M. (2021). A MET Targeting Antibody-Drug Conjugate Overcomes Gemcitabine Resistance in Pancreatic Cancer. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-3210 Cite
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NantKwest, ImmunityBio Announce Positive Interim Data on Survival Rates in Metastatic Pancreatic Cancer Trials

NantKwest, Inc. and ImmunityBio, Inc. announced early interim results of its PD-L1 t-haNK protocols showing median survival rates more than doubled that of the historic rate in patients with advanced metastatic pancreatic cancer for which no other FDA-approved treatment exists.
[NantKwest, Inc.]
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TGFB1/INHBA homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment

The authors focus on TGFB1/INHBA homodimer/Nodal-SMAD2/3 signaling network in pancreatic cancer as a pivotal central node which regulates multiple key mechanisms involved in the development of chemoresistance, including enhancement of the stem cell-like properties and tumorigenicity of pancreatic cancer cells, mediating cooperative interactions between pancreatic cancer cells and the surrounding stroma as well as regulating the deposition of ECM proteins within the tumor microenvironment.
[Molecular Therapy]
Mouti, M. A., & Pauklin, S. (2021). TGFB1/INHBA homodimer/Nodal-SMAD2/3 Signalling Network: A Pivotal Molecular Target in PDAC Treatment. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2021.01.002 Cite
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ABCA8-Mediated Efflux of Taurocholic Acid Contributes to Gemcitabine Insensitivity in Human Pancreatic Cancer via the S1PR2-ERK Pathway

Researchers found that the expression of ABCA8, a member of ABCA subfamily transporters, was significantly increased in human pancreatic cancer (PC) cells after gemcitabine (GEM) treatment, as well as in established GEM-resistant PC cells.
[Cell Death Discovery]
Yang, C., Yuan, H., Gu, J., Xu, D., Wang, M., Qiao, J., Yang, X., Zhang, J., Yao, M., Gu, J., Tu, H., & Gan, Y. (2021). ABCA8-mediated efflux of taurocholic acid contributes to gemcitabine insensitivity in human pancreatic cancer via the S1PR2-ERK pathway. Cell Death Discovery, 7(1), 1–12. https://doi.org/10.1038/s41420-020-00390-z Cite
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The EGFR-HSF1 Axis Accelerates the Tumorigenesis of Pancreatic Cancer

Investigators clarified the mechanisms on early activation of heat shock factor 1 (HSF1) and its role in the pancreatic cancer tumorigenesis.
[Journal of Experimental & Clinical Cancer Research]
Qian, W., Chen, K., Qin, T., Xiao, Y., Li, J., Yue, Y., Zhou, C., Ma, J., Duan, W., Lei, J., Han, L., Li, L., Shen, X., Wu, Z., Ma, Q., & Wang, Z. (2021). The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer. Journal of Experimental & Clinical Cancer Research, 40(1), 25. https://doi.org/10.1186/s13046-020-01823-4 Cite
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Targeting STAT3 by a Small Molecule Suppresses Pancreatic Cancer Progression

Researchers report a new small-molecule inhibitor with potent antitumor bioactivity, which inhibited multiple oncogenic processes in pancreatic cancer.
[Oncogene]
Chen, H., Bian, A., Yang, L., Yin, X., Wang, J., Ti, C., Miao, Y., Peng, S., Xu, S., Liu, M., Qiu, W.-W., & Yi, Z. (2021). Targeting STAT3 by a small molecule suppresses pancreatic cancer progression. Oncogene, 1–18. https://doi.org/10.1038/s41388-020-01626-z Cite
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Zinc Dependent Regulation of ZEB1 and YAP1 Co-Activation Promotes EMT Plasticity and Metastasis in Pancreatic Cancer

Scientists demonstrated that ZIP4 activated ZEB1 and YAP1 through distinct mechanisms. The ZIP4-miR-373-LATS2-ZEB1/YAP1-ITGA3 signaling axis has a significant impact on pancreatic cancer metastasis and EMT plasticity.
[Gastroenterology]
Liu, M., Zhang, Y., Yang, J., Zhan, H., Zhou, Z., Jiang, Y., Shi, X., Fan, X., Zhang, J., Luo, W., Fung, K.-M. A., Xu, C., Bronze, M. S., Houchen, C. W., & Li, M. (2021). Zinc Dependent Regulation of ZEB1 and YAP1 Co-activation Promotes EMT Plasticity and Metastasis in Pancreatic Cancer. Gastroenterology, 0(0). https://doi.org/10.1053/j.gastro.2020.12.077 Cite
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Assessing ZNF154 Methylation in Patient Plasma as a Multicancer Marker in Liquid Biopsies from Colon, Liver, Ovarian and Pancreatic Cancer Patients

Investigators assessed the effectiveness of hypermethylation at the CpG island of ZNF154, a previously reported multi-cancer specific signature for use in a blood-based cancer detection assay.
[Scientific Reports]
Miller, B. F., Petrykowska, H. M., & Elnitski, L. (2021). Assessing ZNF154 methylation in patient plasma as a multicancer marker in liquid biopsies from colon, liver, ovarian and pancreatic cancer patients. Scientific Reports, 11(1), 221. https://doi.org/10.1038/s41598-020-80345-7 Cite
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