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.
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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
Lantheus Holdings, Inc. has announced the submission of a New Drug Application to the US FDA for PyL™, a prostate specific membrane antigen-targeted positron emission tomography imaging agent for prostate cancer.
[Lantheus Holdings, Inc.]
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Scientists demonstrated that HOX transcript antisense RNA (HOTAIR) promoted invasion and metastasis of PCa by decreasing the inhibitory effect of hepaCAM on MAPK signaling. Therefore, the HOTAIR/hepaCAM/MAPK axis may provide a new avenue towards therapeutic strategies and prognostic indicators for advanced prostate cancer.
[British Journal of Cancer]
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Long noncoding RNA HOTAIR regulates the invasion and metastasis of prostate cancer by targeting hepaCAM | British Journal of Cancer. (n.d.). Retrieved October 7, 2020, from https://www.nature.com/articles/s41416-020-01091-1 Cite
Resistance to cancer therapy is a major barrier to cancer management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance, the latter of which is the focus that is discussed here.
[Signal Transduction and Targeted Therapy]
Scientists demonstrated de novo neuroendocrine differentiation of the human prostate luminal epithelial cells induced by caAKT1 and c-Myc and revealed an impact of cellular status on initiation of lineage plasticity.
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Researchers utilized baseline blood samples to identify mCRPC patients most likely to benefit from abiraterone plus prednisone (AAP) or enzalutamide.
[Prostate Cancer and Prostatic Diseases]
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Haas, N. B., LaRiviere, M. J., Buckingham, T. H., Cherkas, Y., Calara-Nielsen, K., Foulk, B., Patel, J., Gross, S., Smirnov, D., Vaughn, D. J., Amaravadi, R., Wellen, K. E., Savitch, S. L., Majmundar, K. J., Black, T. A., Yee, S. S., He, M., Min, E. J., Long, Q., … Carpenter, E. L. (2020). Blood-based gene expression signature associated with metastatic castrate-resistant prostate cancer patient response to abiraterone plus prednisone or enzalutamide. Prostate Cancer and Prostatic Diseases, 1–9. https://doi.org/10.1038/s41391-020-00295-z Cite
Laboratory studies were carried out in human mCRPC organoid cultures, prostate cancer cell lines, and mouse xenograft models. Epigenetic studies were carried out in a rapid autopsy cohort.
[JCO Precision Oncology]
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Wise, D. R., Schneider, J. A., Armenia, J., Febles, V. A., McLaughlin, B., Brennan, R., Thoren, K. L., Abida, W., Sfanos, K. S., De Marzo, A. M., Yegnasubramanian, S., Fox, J. J., Haas, M., Heath, H., Kagey, M. H., Newman, W., Sirard, C. A., Fleisher, M., Morris, M. J., … Sawyers, C. L. (2020). Dickkopf-1 Can Lead to Immune Evasion in Metastatic Castration-Resistant Prostate Cancer. JCO Precision Oncology, 4, 1167–1179. https://doi.org/10.1200/PO.20.00097 Cite
Investigators found that in prostate cancer (PCa), samples from men treated with androgen deprivation therapy, ERβ, and inositol-polyphosphate 4-phosphatase type II (INPP4B) expression were maintained in some samples. To investigate the role of ERβ1 in regulation of INPPB, they engineered the highly metastatic PCa cell line, PC3, to express ERβ1.
[Proceedings of the National Academy of Sciences of the United States of America]
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Chaurasiya, S., Wu, W., Strom, A. M., Warner, M., & Gustafsson, J.-Å. (2020). Estrogen receptor β regulates AKT activity through up-regulation of INPP4B and inhibits migration of prostate cancer cell line PC-3. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2007160117 Cite
Transplantation of CD63-Antares2-expressing prostate cancer cells into mice allowed determining the amount of cancer-derived exosomes released from primary tumors into the bloodstream and visualizing the long-term homing behavior of exosomes to their target organs or tissues.
Researchers demonstrated that protein arginine methyltransferase 5 (PRMT5) functions as an epigenetic activator of androgen receptor transcription in castration-resistant prostate cancer, requiring cooperation with a methylosome subunit pICln.
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Beketova, E., Fang, S., Owens, J. L., Liu, S., Chen, X., Zhang, Q., Asberry, A. M., Deng, X., Malola, J., Huang, J., Li, C., Pili, R., Elzey, B. D., Ratliff, T. L., Wan, J., & Hu, C.-D. (2020). Protein arginine methyltransferase 5 promotes pICln-dependent androgen receptor transcription in castration-resistant prostate cancer. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-1228 Cite
Veru Inc. has announced that it has fully enrolled its Phase II clinical study of VERU-111, its novel, oral, alpha and beta tubulin targeting drug for metastatic castration and novel androgen receptor targeting agent resistant prostate cancer. The study enrolled a total of 40 men at 13 clinical sites in the US.