Response Prediction Biomarkers and Drug Combinations of PARP Inhibitors in Prostate Cancer

Scientists provide an overview of the potential response prediction biomarkers and synergistic combinations studied in the preclinical and clinical stages, which may expand the population of patients with prostate cancer who may benefit from PARP inhibitors.
[Acta Pharmacologica Sinica]
Chen, Y., Tan, L., Gong, J., Huang, M., Yin, J., Zhang, W., Zhou, H., & Liu, Z. (2021). Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer. Acta Pharmacologica Sinica, 1–11. https://doi.org/10.1038/s41401-020-00604-1 Cite
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SWATH-MS Based Proteomic Profiling of Prostate Cancer Cells Reveals Adaptive Molecular Mechanisms in Response to Anti-Androgen Therapy

Scientists interrogated both proteomics and transcriptomic alterations stimulated in AR antagonist/anti-androgen treated androgen-dependent cell model in comparison with androgen-independent/castration-resistant cell model.
[Cancers]
Liyanage, C., Malik, A., Abeysinghe, P., Clements, J., & Batra, J. (2021). SWATH-MS Based Proteomic Profiling of Prostate Cancer Cells Reveals Adaptive Molecular Mechanisms in Response to Anti-Androgen Therapy. Cancers, 13(4), 715. https://doi.org/10.3390/cancers13040715 Cite
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The Mechanics of Prostate Cancer Progression: Toward Characterizing Metastatic Potential as a Function of Cell Contractility

Scientists studied prostate cancer contractility as a function of microenvironment stiffness and metastatic potential.
[Biophysical Journal]
Molter, C. W., & Ehrlicher, A. J. (2021). The Mechanics of Prostate Cancer Progression: Toward Characterizing Metastatic Potential as a Function of Cell Contractility. Biophysical Journal, 120(3), 168a. https://doi.org/10.1016/j.bpj.2020.11.1192 Cite
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Macrophages Support the Aggressive Mechanical Phenotype of Circulating Tumor Cells in Prostate Cancer

Investigators recapitulated the tumor cells – macrophages interactions in cell culture using prostate cancer cell lines.
[Biophysical Journal]
Osmulski, P. A., Cunsolo, A., Qian, Y., Chen, M., Lin, C.-L., Hung, C.-N., Mahalingam, D., Kirma, N., Chen, C.-L., Taverna, J., Liss, M., Thompson, I. M., Huang, T. H., & Gaczynska, M. (2021). Macrophages Support the Aggressive Mechanical Phenotype of Circulating Tumor Cells in Prostate Cancer. Biophysical Journal, 120(3), 64a–65a. https://doi.org/10.1016/j.bpj.2020.11.619 Cite
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66Ga-PET-Imaging of GRPR-Expression in Prostate Cancer: Production and Characterization of [66Ga]Ga-NOTA-PEG2-RM26

Researchers produced gallium-66 suitable for radiolabeling, and investigated the imaging properties of gallium-66 labeled gastrin-releasing peptide receptor (GRPR)-antagonist NOTA-PEG2-RM26 for later-time point PET-imaging of GRPR expression. In vitro, [66Ga]Ga-NOTA-PEG2-RM26 was characterized in GRPR-expressing PC-3 prostate cancer cells.
[Scientific Reports]
Rinne, S. S., Abouzayed, A., Gagnon, K., Tolmachev, V., & Orlova, A. (2021). 66 Ga-PET-imaging of GRPR-expression in prostate cancer: production and characterization of [ 66 Ga]Ga-NOTA-PEG 2 -RM26. Scientific Reports, 11(1), 3631. https://doi.org/10.1038/s41598-021-82995-7 Cite
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Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells

Researchers explored whether the anti-prostate cancer activity of the ARATs abiraterone and enzalutamide was enhanced by metformin.
[Cancers]
Xie, Y., Wang, L., Khan, M. A., Hamburger, A. W., Guang, W., Passaniti, A., Munir, K., Ross, D. D., Dean, M., & Hussain, A. (2021). Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells. Cancers, 13(4), 633. https://doi.org/10.3390/cancers13040633 Cite
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V-ATPase Inhibition Decreases Mutant Androgen Receptor Activity in Castrate-Resistant Prostate Cancer

Investigators indicated that V-ATPase dysregulation was directly linked to both hormone responsive and castrate-resistant prostate cancer via impact on androgen receptor function.
[Molecular Cancer Therapeutics]
Whitton, B., Okamoto, H., Rose-Zerilli, M., Packham, G., & Crabb, S. J. (2021). V-ATPase inhibition decreases mutant androgen receptor activity in castrate-resistant prostate cancer. Molecular Cancer Therapeutics. https://doi.org/10.1158/1535-7163.MCT-20-0662 Cite
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Janssen Announces Treatment with ERLEADA® (Apalutamide) Significantly Improved Overall Survival in Patients with Metastatic Castration-Sensitive Prostate Cancer

The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from the final analysis of the Phase III TITAN study, which demonstrated the continued statistically significant benefit of the addition of apalutamide to androgen deprivation therapy (ADT) in overall survival in patients with metastatic castration-sensitive prostate cancer, regardless of extent of disease, when compared to placebo plus ADT.
[Janssen Pharmaceutical Companies of Johnson & Johnson]
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ZRSR2 Overexpression Is a Frequent and Early Event in Castration-Resistant Prostate Cancer Development

Scientists identified potential early driver genes responsible for castration-resistant prostate cancer development.
[Prostate Cancer and Prostatic Diseases]
He, H., Hao, J., Dong, X., Wang, Y., Xue, H., Qu, S., Choi, S. Y. C., Ci, X., Wang, Y., Wu, R., Shi, M., Zhao, X., Collins, C., Lin, D., & Wang, Y. (2021). ZRSR2 overexpression is a frequent and early event in castration-resistant prostate cancer development. Prostate Cancer and Prostatic Diseases, 1–11. https://doi.org/10.1038/s41391-021-00322-7 Cite
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Clinical Considerations for the Management of Androgen Indifferent Prostate Cancer

The authors summarize the current knowledge on androgen indifferent prostate cancer (AIPC) variants, including the current understanding of the clinical, morphologic, and molecular features as well as current therapeutic approaches. They also explore emerging therapies and biomarkers aimed at improving outcomes for men with AIPC.
[Prostate Cancer and Prostatic Diseases]
Berchuck, J. E., Viscuse, P. V., Beltran, H., & Aparicio, A. (2021). Clinical considerations for the management of androgen indifferent prostate cancer. Prostate Cancer and Prostatic Diseases, 1–15. https://doi.org/10.1038/s41391-021-00332-5 Cite
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Long-Chain Fatty Acyl-CoA Synthetase 1 Promotes Prostate Cancer Progression by Elevation of Lipogenesis and Fatty Acid Beta-oxidation

A systematical analysis of long-chain fatty acyl-CoA synthetases (ACSLs) levels and the amount of fatty acyl-CoAs illustrated that ACSL1 were significantly associated with the levels of a broad spectrum of fatty acyl-CoAs, and were elevated in human prostate tumors.
[Oncogene]
Ma, Y., Zha, J., Yang, X., Li, Q., Zhang, Q., Yin, A., Beharry, Z., Huang, H., Huang, J., Bartlett, M., Ye, K., Yin, H., & Cai, H. (2021). Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation. Oncogene, 1–15. https://doi.org/10.1038/s41388-021-01667-y Cite
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