Regulation of CEACAM5 and Therapeutic Efficacy of an Anti-CEACAM5-SN38 Antibody-Drug Conjugate in Neuroendocrine Prostate Cancer

Scientists investigated the scope of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression in end-stage prostate cancer, the basis for CEACAM5 enrichment in euroendocrine prostate cancer, and the therapeutic potential of the CEACAM5 antibody-drug conjugate labetuzumab govitecan in prostate cancer.
[Clinical Cancer Research]
DeLucia, D. C., Cardillo, T. M., Ang, L. S., Labrecque, M. P., Zhang, A., Hopkins, J. E., Sarkar, N. D., Coleman, I., Costa, R. M. G. da, Corey, E., True, L. D., Haffner, M. C., Schweizer, M. T., Morrissey, C., Nelson, P. S., & Lee, J. K. (2020). Regulation of CEACAM5 and therapeutic efficacy of an anti-CEACAM5-SN38 antibody-drug conjugate in neuroendocrine prostate cancer. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-3396 Cite
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Patient-Derived Tumor Models for Personalized Therapeutics in Urological Cancers

Preclinical knowledge of dysregulated pathways and potential biomarkers for urological cancers has undergone limited translation into the clinic. Moreover, the low approval rate of new anticancer drugs and the heterogeneous drug responses in patients indicate that current preclinical models do not always reflect the complexity of malignant disease.
[Nature Reviews Urology]
van de Merbel, A. F., van der Horst, G., & van der Pluijm, G. (2020). Patient-derived tumour models for personalized therapeutics in urological cancers. Nature Reviews Urology, 1–13. https://doi.org/10.1038/s41585-020-00389-2 Cite
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IL-6 Trans-Signaling Promotes the Expansion and Anti-Tumor Activity of CAR T Cells

Hyper IL-6-expressing CAR T-cells exhibited enhanced proliferation and antitumor efficacy in vitro and in xenograft models.
[Leukemia]
Jiang, Z., Liao, R., Lv, J., Li, S., Zheng, D., Qin, L., Wu, D., Chen, S., Long, Y., Wu, Q., Wang, S., Lin, S., Huang, X., Tang, Z., Shi, P., Zhou, H., Liu, Q., Zhao, R., Li, Y., … Li, P. (2020). IL-6 trans-signaling promotes the expansion and anti-tumor activity of CAR T cells. Leukemia, 1–12. https://doi.org/10.1038/s41375-020-01085-1 Cite
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Expression of the Chemokine Receptor CCR1 Promotes the Dissemination of Multiple Myeloma Plasma Cells In Vivo

Scientists demonstrated that CCR1 expression was an independent prognostic indicator in newly diagnosed multiple myeloma patients.
[Haematologica]
Zeissig, M. N., Hewett, D. R., Panagopoulos, V., Mrozik, K. M., To, L. B., Croucher, P. I., Zannettino, A. C. W., & Vandyke, K. (2020). Expression of the chemokine receptor CCR1 promotes the dissemination of multiple myeloma plasma cells <em>in vivo</em>. Haematologica, 0–0. https://doi.org/10.3324/haematol.2020.253526 Cite
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BRCA1 and BRCA2 Associated Breast Cancer and the Roles of Current Modeling Systems in Drug Discovery

The authors discuss BRCA1 and BRCA2 cancer biology and current modeling systems that will guide the design of future drug discovery endeavors and highlight areas requiring improvement.
[Biochimica et Biophysica Acta-Reviews on Cancer]
Trusler, O., Goodwin, J., & Laslett, A. L. (2020). BRCA1 and BRCA2 associated breast cancer and the roles of current modelling systems in drug discovery. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 188459. https://doi.org/10.1016/j.bbcan.2020.188459 Cite
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Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B Axis Facilitates Prostate Cancer Progression

The expression of lysine-specific demethylase 5 A (KDM5A), miR-495, YTHDF2 and MOB3B was validated in human prostate cancer (PCa) tissues and cell lines. Ectopic expression and knockdown experiments were developed in PCa cells to evaluate their effects on PCa cell proliferation, migration, invasion and apoptosis.
[Journal of Experimental & Clinical Cancer Research]
Du, C., Lv, C., Feng, Y., & Yu, S. (2020). Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression. Journal of Experimental & Clinical Cancer Research, 39(1), 223. https://doi.org/10.1186/s13046-020-01735-3 Cite
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Hepatocellular Carcinoma with PARP1 and DNA-PK Inhibitors

Combining olaparib with NU7441, a DNA-PKcs inhibitor that blocks nonhomologous end-joining in hepatocellular carcinoma (HCC), synergistically suppressed HCC growth in both mice and HCC patient-derived-xenograft models.
[Proceedings of the National Academy of Sciences of the United States of America]
Wang, C., Tang, H., Geng, A., Dai, B., Zhang, H., Sun, X., Chen, Y., Qiao, Z., Zhu, H., Yang, J., Chen, J., He, Q., Qin, N., Xie, J., Tan, R., Wan, X., Gao, S., Jiang, Y., Sun, F.-L., & Mao, Z. (2020). Rational combination therapy for hepatocellular carcinoma with PARP1 and DNA-PK inhibitors. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2002917117 Cite
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Short Term CDK4/6 Inhibition Radiosensitizes Estrogen Receptor Positive Breast Cancers

Researchers sought to understand the effects of CDK4/6 inhibition and radiation in multiple preclinical breast cancer models.
[Clinical Cancer Research]
Pesch, A. M., Hirsh, N., Chandler, B. C., Michmerhuizen, A. R., Ritter, C. L., Androsiglio, M., Wilder-Romans, K., Liu, M., Gersch, C., Larios, J. M., Pierce, L. J., Rae, J. M., & Speers, C. (2020). Short Term CDK4/6 Inhibition Radiosensitizes Estrogen Receptor Positive Breast Cancers. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-2269 Cite
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Transient IGF-1R Inhibition Combined with Osimertinib Eradicates AXL-Low Expressing EGFR Mutated Lung Cancer

Scientists showed that while AXL-low expressing epidermal growth factor receptor mutated lung cancer (EGFRmut-LC) cells were more sensitive to osimertinib than AXL-high expressing EGFRmut-LC cells, a small population emerge osimertinib tolerance.
[Nature Communications]
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5-Fluorouracil Enhances the Anti-Tumor Activity of the Glutaminase Inhibitor CB-839 against PIK3CA-Mutant Colorectal Cancers

Investigators report that the glutaminase inhibitor CB-839 preferentially inhibited xenograft growth of PIK3CA-mutant, but not wild-type, colorectal cancer. Moreover, the combination of CB-839 and 5-fluorouracil induces PIK3CA-mutant tumor regression in xenograft models.
[Cancer Research]
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CSPG4-Specific CAR.CIK Lymphocytes as a Novel Therapy for the Treatment of Multiple Soft Tissue Sarcoma Histotypes

The functional activity of chondroitin sulfate proteoglycan 4 (CSPG4)-CAR-redirected cytokine-induced killer lymphocytes (CAR.CIK) was explored in vitro, in 2D and 3D soft tissue sarcoma (STS) cultures, and in three in vivo STS xenograft models.
[Clinical Cancer Research]
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