The authors demonstrated that tumor-infiltrating γδ T cells isolated from patients with ovarian cancer have distinct T cell receptors and exhibit more innate-like functions compared to blood- or ascites-derived γδ T cells.
[Science Translational Medicine]
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The authors examined whether three commonly prescribed selective serotonin reuptake inhibitors (SSRIs), fluoxetine, sertraline and citalopram, affected proliferation or glucose uptake of human breast and ovarian cancer cell lines characterized by different malignancies and metastatic potential.
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Zentalis Pharmaceuticals, Inc. announced that the company has initiated patient dosing in three new combination and monotherapy clinical trials.
[Zentalis Pharmaceuticals, Inc.]
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Tumor-reactive tumor-infiltrating lymphocytes were detected in half of patients and were exclusively present in cells derived from the PD-1+ fraction.
[British Journal of Cancer]
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Salas-Benito, D., Conde, E., Tamayo-Uria, I., Mancheño, U., Elizalde, E., Garcia-Ros, D., Aramendia, J. M., Muruzabal, J. C., Alcaide, J., Guillen-Grima, F., Minguez, J. A., Amores-Tirado, J., Gonzalez-Martin, A., Sarobe, P., Lasarte, J. J., Ponz-Sarvise, M., De Andrea, C. E., & Hervas-Stubbs, S. (2021). The mutational load and a T-cell inflamed tumour phenotype identify ovarian cancer patients rendering tumour-reactive T cells from PD-1 + tumour-infiltrating lymphocytes. British Journal of Cancer, 1–12. https://doi.org/10.1038/s41416-020-01218-4 Cite
Scientists present the results of repeated intratumoral injections of AdCD40L in seven patients with metastatic solid cancer.
[Cancer Gene Therapy]
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Irenaeus, S., Hellström, V., Wenthe, J., Krause, J., Sundin, A., Ahlström, H., Tufveson, G., Tötterman, T. H., Loskog, A., & Ullenhag, G. J. (2020). Intratumoral immunostimulatory AdCD40L gene therapy in patients with advanced solid tumors. Cancer Gene Therapy, 1–10. https://doi.org/10.1038/s41417-020-00271-8 Cite
The effects and molecular mechanisms of ASC‐J9 on various AR‐associated diseases are summarized. Importantly, the effects of ASC‐J9 and AR antagonists enzalutamide/bicalutamide on prostate cancer are compared in detail and crucial differences are highlighted.
[Chemical Biology & Drug Design]
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Hu, H., Zhou, H., & Xu, D. (n.d.). A review of the effects and molecular mechanisms of dimethylcurcumin (ASC-J9) on androgen receptor-related diseases. Chemical Biology & Drug Design, n/a(n/a). https://doi.org/https://doi.org/10.1111/cbdd.13811 Cite
Harpoon Therapeutics, Inc. has provided a pipeline update and reported a confirmed partial response based on RECIST v1.1 criteria for its most advanced program, HPN424 for the treatment of metastatic castration-resistant prostate cancer. In the 160ng/kg cohort, which is the highest fixed dose tested to date, seven patients have been enrolled and one patient has achieved a confirmed partial response.
[Harpoon Therapeutics, Inc.]
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The authors show that, in addition to cancer cell epithelial-to-mesenchymal transition, ovarian cancer cell metastasis relies on an epigenomic mesenchymal-to-epithelial transition in host MSCs. These reprogrammed MSCs, termed carcinoma-associated MSCs, acquire pro-tumorigenic functions and directly bind cancer cells to serve as a metastatic driver/chaperone.
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Fan, H., Atiya, H. I., Wang, Y., Pisanic, T. R., Wang, T.-H., Shih, I.-M., Foy, K. K., Frisbie, L., Buckanovich, R. J., Chomiak, A. A., Tiedemann, R. L., Rothbart, S. B., Chandler, C., Shen, H., & Coffman, L. G. (2020). Epigenomic Reprogramming toward Mesenchymal-Epithelial Transition in Ovarian-Cancer-Associated Mesenchymal Stem Cells Drives Metastasis. Cell Reports, 33(10). https://doi.org/10.1016/j.celrep.2020.108473 Cite
The authors demonstrated that tumor-derived UBR5, an E3 ligase overexpressed in human ovarian cancer (OC) associated with poor prognosis, was essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines.
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Song, M., Yeku, O. O., Rafiq, S., Purdon, T., Dong, X., Zhu, L., Zhang, T., Wang, H., Yu, Z., Mai, J., Shen, H., Nixon, B., Li, M., Brentjens, R. J., & Ma, X. (2020). Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages. Nature Communications, 11(1), 6298. https://doi.org/10.1038/s41467-020-20140-0 Cite
The microenvironment possesses a strong impact on the tumor chemoresistance when cells bind to components of the ECM. Scientists elucidated the signaling pathways of cisplatin resistance in W1 ovarian cancer cells binding to collagen type 1 and signaling interference with constitutive cisplatin resistance in W1CR cells to discover the targets for sensitization.
[International Journal of Molecular Sciences]
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Wantoch von Rekowski, K., König, P., Henze, S., Schlesinger, M., Zawierucha, P., Januchowski, R., & Bendas, G. (2020). Insight into Cisplatin-Resistance Signaling of W1 Ovarian Cancer Cells Emerges mTOR and HSP27 as Targets for Sensitization Strategies. International Journal of Molecular Sciences, 21(23), 9240. https://doi.org/10.3390/ijms21239240 Cite
The authors expand on the clinical development of PARP inhibitors (PARPis) in metastatic castration-resistant prostate cancer, discuss potential biomarkers that may predict successful tumor control, and summarize present and future clinical research on PARPis in the metastatic disease landscape.