Journal of Computational Applied Mechanics
Effects of substrate stiffness and anti-cancer drug on morphology and viability of Prostate cancer cell lines
Document Type : Research Paper
Authors
1 Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran
2 Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran
Abstract
Cancer cell detection in various tissues of the body, as well as during chemical medication treatment, can aid in identifying these cells and providing faster and more effective treatments. Studies have been conducted to aid in the diagnosis and identification of cancer cells. Although significant progress has been made, there is still a need for research in this sector, particularly when multiple variables are considered at the same time. The present study has the novelty of examining the simultaneous effects of cell culture substrates and chemical drugs on the morphology of two cancer cell lines with different degrees of invasion. In the current study, two cell lines with varying degrees of metastasis were cultivated on three surfaces with varying elastic modulus, and their morphology was studied using photography and image processing with code and software. In this study, the cell morphology was evaluated with great precision. In addition, the cell viability of these two cell lines was assessed for the aforementioned groups in order to determine the rate of cell death in each group. The findings show that drugs have a greater impact on cell morphology than substrates and cell types, and that the two cell lines respond differently to drug and substrate combinations, with DU145 cells being more susceptible to drug-induced cytotoxic effects. primarily on soft substrates. Understanding these interactions is critical for adapting treatments to the specific properties of prostate cancer cells, which could improve outcomes for patients with various metastatic tendencies.
Keywords
Main Subjects
[1] S. Iyer, R. Gaikwad, V. Subba-Rao, C. Woodworth, I. Sokolov, Atomic force microscopy detects differences in the surface brush of normal and cancerous cells, Nature nanotechnology, Vol. 4, No. 6, pp. 389-393, 2009.
[2] C.-H. Hsieh, Y.-H. Lin, S. Lin, J.-J. Tsai-Wu, C. H. Wu, C.-C. Jiang, Surface ultrastructure and mechanical property of human chondrocyte revealed by atomic force microscopy, Osteoarthritis and cartilage, Vol. 16, No. 4, pp. 480-488, 2008.
[3] K. Dastani, M. Moghimi Zand, A. Hadi, Dielectrophoretic effect of nonuniform electric fields on the protoplast cell, Journal of Computational Applied Mechanics, Vol. 48, No. 1, pp. 1-14, 2017.
[4] D. Vignjevic, G. Montagnac, Reorganisation of the dendritic actin network during cancer cell migration and invasion, in Proceeding of, Elsevier, pp. 12-22.
[5] A. Kordzadeh, S. Javdansirat, N. Javdansirat, H. Tang, S. Ghaderi, A. Hadi, R. Mahmoudi, M. Nikseresht, Investigating Heat-Induced Phase Transitions in POPC Lipid Bilayers Using Molecular Dynamics Simulations, Journal of Computational Applied Mechanics, Vol. 55, No. 4, pp. 771-782, 2024.
[6] N. Miyoshi, H. Tanabe, T. Suzuki, K. Saeki, Y. Hara, Applications of a standardized green tea catechin preparation for viral warts and human papilloma virus-related and unrelated cancers, Molecules, Vol. 25, No. 11, pp. 2588, 2020.
[7] S. K. Tyring, Effect of Sinecatechins on HPV-Activated Cell Growth and Induction of Apoptosis, J Clin Aesthet Dermatol, Vol. 5, No. 2, pp. 34-41, Feb, 2012. eng
[8] Y. Hara, Tea catechins and their applications as supplements and pharmaceutics, Pharmacol Res, Vol. 64, No. 2, pp. 100-4, Aug, 2011. eng
[9] M. S. Chapekar, Tissue engineering: challenges and opportunities, Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, Vol. 53, No. 6, pp. 617-620, 2000.
[10] T.-H. Chang, H.-D. Huang, W.-K. Ong, Y.-J. Fu, O. K. Lee, S. Chien, J. H. Ho, The effects of actin cytoskeleton perturbation on keratin intermediate filament formation in mesenchymal stem/stromal cells, Biomaterials, Vol. 35, No. 13, pp. 3934-3944, 2014.
[11] D. Lü, C. Luo, C. Zhang, Z. Li, M. Long, Differential regulation of morphology and stemness of mouse embryonic stem cells by substrate stiffness and topography, Biomaterials, Vol. 35, No. 13, pp. 3945-3955, 2014/04/01/, 2014.
[12] L. Trichet, J. Le Digabel, R. J. Hawkins, S. R. K. Vedula, M. Gupta, C. Ribrault, P. Hersen, R. Voituriez, B. Ladoux, Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness, Proceedings of the National Academy of Sciences, Vol. 109, No. 18, pp. 6933-6938, 2012.
[13] N. Mahmoodi, J. Ai, Z. Hassannejad, S. Ebrahimi-Barough, E. Hasanzadeh, A. Hadi, H. Nekounam, V. Rahimi-Movaghar, Are reported methods for synthesizing nanoparticles and microparticles by magnetic stirrer reproducible?, Journal of Computational Applied Mechanics, Vol. 51, No. 2, pp. 498-500, 2020.
[14] A. Korolj, C. Laschinger, C. James, E. Hu, C. Velikonja, N. Smith, I. Gu, S. Ahadian, R. Willette, M. Radisic, Curvature facilitates podocyte culture in a biomimetic platform, Lab on a Chip, Vol. 18, No. 20, pp. 3112-3128, 2018.
[15] P. A. Janmey, R. T. Miller, Mechanisms of mechanical signaling in development and disease, Journal of cell science, Vol. 124, No. 1, pp. 9-18, 2011.
[16] S. R. Caliari, J. A. Burdick, A practical guide to hydrogels for cell culture, Nature methods, Vol. 13, No. 5, pp. 405-414, 2016.
[17] K. Lee, F. Forudi, G. M. Saidel, M. S. Penn, Alterations in internal elastic lamina permeability as a function of age and anatomical site precede lesion development in apolipoprotein E–null mice, Circulation research, Vol. 97, No. 5, pp. 450-456, 2005.
[18] M. CM, Normal vascular aging: Differential effects on wave reflection and aortic pulse wave velocity, J Am Coll Cardiol, Vol. 46, pp. 1753-1760, 2005.
[19] S. R. Ramezani, A. Mojra, M. Tafazzoli-Shadpour, Investigating the effects of substrate stiffness on half-maximal inhibitory concentration of chemical anticancer drugs, cell viability and migration of cell lines, Cellular, Molecular and Biomedical Reports, pp. 141-147, 2024.
[20] S. Au - Syed, A. Au - Karadaghy, S. Au - Zustiak, Simple Polyacrylamide-based Multiwell Stiffness Assay for the Study of Stiffness-dependent Cell Responses, JoVE, No. 97, pp. e52643, 2015/03/25/, 2015.
[21] R. G. Wells, The role of matrix stiffness in regulating cell behavior, Hepatology, Vol. 47, No. 4, pp. 1394-1400, 2008.
[22] Q. Chai, Y. Jiao, X. Yu, Hydrogels for biomedical applications: their characteristics and the mechanisms behind them, Gels, Vol. 3, No. 1, pp. 6, 2017.
[23] E. Caló, V. V. Khutoryanskiy, Biomedical applications of hydrogels: A review of patents and commercial products, European polymer journal, Vol. 65, pp. 252-267, 2015.
[24] M. Bassil, J. Davenas, M. E. Tahchi, Electrochemical properties and actuation mechanisms of polyacrylamide hydrogel for artificial muscle application, Sensors and Actuators B: Chemical, Vol. 134, No. 2, pp. 496-501, 2008.
[25] M. Bassil, M. Ibrahim, M. El Tahchi, Artificial muscular microfibers: hydrogel with high speed tunable electroactivity, Soft Matter, Vol. 7, No. 10, pp. 4833-4838, 2011.
[26] N. Chirani, L. Yahia, L. Gritsch, F. L. Motta, S. Chirani, S. Farè, History and applications of hydrogels, Journal of biomedical sciences, Vol. 4, No. 02, pp. 1-23, 2015.
[27] K. S. Kim, C. H. Cho, E. K. Park, M.-H. Jung, K.-S. Yoon, H.-K. Park, AFM-detected apoptotic changes in morphology and biophysical property caused by paclitaxel in Ishikawa and HeLa cells, PloS one, Vol. 7, No. 1, pp. e30066, 2012.
[28] C.-C. K. Lin, C.-H. Yang, M.-S. Ju, Cytotoxic and biomechanical effects of clinical dosing schemes of paclitaxel on neurons and cancer cells, Cancer Chemotherapy and Pharmacology, Vol. 86, pp. 245-255, 2020.
[29] A. K. Harris, D. Stopak, P. Wild, Fibroblast traction as a mechanism for collagen morphogenesis, Nature, Vol. 290, No. 5803, pp. 249-51, Mar 19, 1981. eng
[30] A. K. Harris, P. Wild, D. Stopak, Silicone rubber substrata: a new wrinkle in the study of cell locomotion, Science, Vol. 208, No. 4440, pp. 177-9, Apr 11, 1980. eng
[31] C. X. Li, N. P. Talele, S. Boo, A. Koehler, E. Knee-Walden, J. L. Balestrini, P. Speight, A. Kapus, B. Hinz, MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells, Nat Mater, Vol. 16, No. 3, pp. 379-389, Mar, 2017. eng
[32] A. Zhong, Z. Mirzaei, C. A. Simmons, The Roles of Matrix Stiffness and ß-Catenin Signaling in Endothelial-to-Mesenchymal Transition of Aortic Valve Endothelial Cells, Cardiovasc Eng Technol, Vol. 9, No. 2, pp. 158-167, Jun, 2018. eng
[33] T. Tzvetkova-Chevolleau, A. Stéphanou, D. Fuard, J. Ohayon, P. Schiavone, P. Tracqui, The motility of normal and cancer cells in response to the combined influence of the substrate rigidity and anisotropic microstructure, Biomaterials, Vol. 29, No. 10, pp. 1541-51, Apr, 2008. eng
[34] Y. Andriani, J. M. Chua, B. Y. Chua, I. Y. Phang, N. Shyh-Chang, W. S. Tan, Polyurethane acrylates as effective substrates for sustained in vitro culture of human myotubes, Acta Biomater, Vol. 57, pp. 115-126, Jul 15, 2017. eng
[35] L. Cacopardo, N. Guazzelli, R. Nossa, G. Mattei, A. Ahluwalia, Engineering hydrogel viscoelasticity, J Mech Behav Biomed Mater, Vol. 89, pp. 162-167, Jan, 2019. eng
[36] E. Migliorini, J. Ban, G. Grenci, L. Andolfi, A. Pozzato, M. Tormen, V. Torre, M. Lazzarino, Nanomechanics controls neuronal precursors adhesion and differentiation, Biotechnol Bioeng, Vol. 110, No. 8, pp. 2301-10, Aug, 2013. eng
[37] C. E. Kandow, P. C. Georges, P. A. Janmey, K. A. Beningo, Polyacrylamide hydrogels for cell mechanics: steps toward optimization and alternative uses, Methods Cell Biol, Vol. 83, pp. 29-46, 2007. eng
[38] T. Okamoto, Y. Takagi, E. Kawamoto, E. J. Park, H. Usuda, K. Wada, M. Shimaoka, Reduced substrate stiffness promotes M2-like macrophage activation and enhances peroxisome proliferator-activated receptor γ expression, Exp Cell Res, Vol. 367, No. 2, pp. 264-273, Jun 15, 2018. eng
[39] P. Zarrintaj, S. Manouchehri, Z. Ahmadi, M. R. Saeb, A. M. Urbanska, D. L. Kaplan, M. Mozafari, Agarose-based biomaterials for tissue engineering, Carbohydr Polym, Vol. 187, pp. 66-84, May 1, 2018. eng
[40] A. Bauer, L. Gu, B. Kwee, W. A. Li, M. Dellacherie, A. D. Celiz, D. J. Mooney, Hydrogel substrate stress-relaxation regulates the spreading and proliferation of mouse myoblasts, Acta Biomater, Vol. 62, pp. 82-90, Oct 15, 2017. eng
[41] M. Bao, J. Xie, N. Katoele, X. Hu, B. Wang, A. Piruska, W. T. S. Huck, Cellular Volume and Matrix Stiffness Direct Stem Cell Behavior in a 3D Microniche, ACS Appl Mater Interfaces, Vol. 11, No. 2, pp. 1754-1759, Jan 16, 2019. eng
[42] T. Yeung, P. C. Georges, L. A. Flanagan, B. Marg, M. Ortiz, M. Funaki, N. Zahir, W. Ming, V. Weaver, P. A. Janmey, Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion, Cell Motil Cytoskeleton, Vol. 60, No. 1, pp. 24-34, Jan, 2005. eng
[43] F. Martino, A. R. Perestrelo, V. Vinarský, S. Pagliari, G. Forte, Cellular Mechanotransduction: From Tension to Function, Front Physiol, Vol. 9, pp. 824, 2018. eng
[44] L. Martinez-Vidal, V. Murdica, C. Venegoni, F. Pederzoli, M. Bandini, A. Necchi, A. Salonia, M. Alfano, Causal contributors to tissue stiffness and clinical relevance in urology, Commun Biol, Vol. 4, No. 1, pp. 1011, Aug 26, 2021. eng
[45] Y. F. I. Setargew, K. Wyllie, R. D. Grant, J. L. Chitty, T. R. Cox, Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours, Cancers (Basel), Vol. 13, No. 3, Jan 27, 2021. eng
[46] M. W. Pickup, J. K. Mouw, V. M. Weaver, The extracellular matrix modulates the hallmarks of cancer, EMBO Rep, Vol. 15, No. 12, pp. 1243-53, Dec, 2014. eng
[47] B. Emon, J. Bauer, Y. Jain, B. Jung, T. Saif, Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review, Comput Struct Biotechnol J, Vol. 16, pp. 279-287, 2018. eng
[48] J. Winkler, A. Abisoye-Ogunniyan, K. J. Metcalf, Z. Werb, Concepts of extracellular matrix remodelling in tumour progression and metastasis, Nat Commun, Vol. 11, No. 1, pp. 5120, Oct 9, 2020. eng
[49] V. Poltavets, M. Kochetkova, S. M. Pitson, M. S. Samuel, The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity, Front Oncol, Vol. 8, pp. 431, 2018. eng
[50] N. M. Anderson, M. C. Simon, The tumor microenvironment, Curr Biol, Vol. 30, No. 16, pp. R921-r925, Aug 17, 2020. eng
[51] T. R. Cox, The matrix in cancer, Nat Rev Cancer, Vol. 21, No. 4, pp. 217-238, Apr, 2021. eng
[52] A. M. Socovich, A. Naba, The cancer matrisome: From comprehensive characterization to biomarker discovery, Semin Cell Dev Biol, Vol. 89, pp. 157-166, May, 2019. eng
[53] K. R. Levental, H. Yu, L. Kass, J. N. Lakins, M. Egeblad, J. T. Erler, S. F. Fong, K. Csiszar, A. Giaccia, W. Weninger, M. Yamauchi, D. L. Gasser, V. M. Weaver, Matrix crosslinking forces tumor progression by enhancing integrin signaling, Cell, Vol. 139, No. 5, pp. 891-906, Nov 25, 2009. eng
[54] C. Ricciardelli, D. L. Russell, M. P. Ween, K. Mayne, S. Suwiwat, S. Byers, V. R. Marshall, W. D. Tilley, D. J. Horsfall, Formation of hyaluronan- and versican-rich pericellular matrix by prostate cancer cells promotes cell motility, J Biol Chem, Vol. 282, No. 14, pp. 10814-25, Apr 6, 2007. eng
[55] W. D. Ni, Z. T. Yang, C. A. Cui, Y. Cui, L. Y. Fang, Y. H. Xuan, Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer, Biochem Biophys Res Commun, Vol. 486, No. 3, pp. 607-612, May 6, 2017. eng
[56] B. F. Gonçalves, S. G. Campos, C. F. Costa, W. R. Scarano, R. M. Góes, S. R. Taboga, Key participants of the tumor microenvironment of the prostate: an approach of the structural dynamic of cellular elements and extracellular matrix components during epithelial-stromal transition, Acta Histochem, Vol. 117, No. 1, pp. 4-13, Jan, 2015. eng
[57] M. P. Caley, H. King, N. Shah, K. Wang, M. Rodriguez-Teja, J. H. Gronau, J. Waxman, J. Sturge, Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces, Clin Exp Metastasis, Vol. 33, No. 2, pp. 151-65, Feb, 2016. eng
[58] Z. Liu, L. Wang, H. Xu, Q. Du, L. Li, L. Wang, E. S. Zhang, G. Chen, Y. Wang, Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns, Adv Sci (Weinh), Vol. 7, No. 15, pp. 1903583, Aug, 2020. eng
[59] K. M. Aw Yong, Y. Sun, S. D. Merajver, J. Fu, Mechanotransduction-Induced Reversible Phenotypic Switching in Prostate Cancer Cells, Biophys J, Vol. 112, No. 6, pp. 1236-1245, Mar 28, 2017. eng
[60] J. L. Eisenberg, A. Safi, X. Wei, H. D. Espinosa, G. S. Budinger, D. Takawira, S. B. Hopkinson, J. C. Jones, Substrate stiffness regulates extracellular matrix deposition by alveolar epithelial cells, Res Rep Biol, Vol. 2011, No. 2, pp. 1-12, Jan, 2011. eng
[61] A. Petersen, P. Joly, C. Bergmann, G. Korus, G. N. Duda, The impact of substrate stiffness and mechanical loading on fibroblast-induced scaffold remodeling, Tissue Eng Part A, Vol. 18, No. 17-18, pp. 1804-17, Sep, 2012. eng
[62] O. V. Sazonova, K. L. Lee, B. C. Isenberg, C. B. Rich, M. A. Nugent, J. Y. Wong, Cell-cell interactions mediate the response of vascular smooth muscle cells to substrate stiffness, Biophys J, Vol. 101, No. 3, pp. 622-30, Aug 3, 2011. eng
[63] Z. Goli-Malekabadi, M. Tafazzoli-Shadpour, A. Tamayol, E. Seyedjafari, Time dependency of morphological remodeling of endothelial cells in response to substrate stiffness, Bioimpacts, Vol. 7, No. 1, pp. 41-47, 2017. eng
[64] X. Tang, Y. Zhang, J. Mao, Y. Wang, Z. Zhang, Z. Wang, H. Yang, Effects of substrate stiffness on the viscoelasticity and migration of prostate cancer cells examined by atomic force microscopy, Beilstein Journal of Nanotechnology, Vol. 13, pp. 560-569, //, 2022.
[65] A. J. McKenzie, S. R. Hicks, K. V. Svec, H. Naughton, Z. L. Edmunds, A. K. Howe, The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation, Scientific Reports, Vol. 8, No. 1, pp. 7228, 2018/05/08, 2018.
[66] Y. Fan, Q. Sun, X. Li, J. Feng, Z. Ao, X. Li, J. Wang, Substrate Stiffness Modulates the Growth, Phenotype, and Chemoresistance of Ovarian Cancer Cells, Frontiers in Cell and Developmental Biology, Vol. 9, 2021-August-24, 2021. English
[67] L. Chen, G. Zhao, M. De Menna, S. Coppola, N. Landman, S. Schieven, A. Groenewoud, G. N. Thalmann, T. Schmidt, J. de Vries, Mechano-signaling of prostate tumor initiating cells facilitates their tropism to stiff metastatic niche, bioRxiv, pp. 2023.08. 28.553410, 2023.
[68] V. Gkretsi, T. Stylianopoulos, Cell adhesion and matrix stiffness: coordinating cancer cell invasion and metastasis, Frontiers in oncology, Vol. 8, pp. 145, 2018.
[69] L. E. Lamb, J. C. Zarif, C. K. Miranti, The androgen receptor induces integrin α6β1 to promote prostate tumor cell survival via NF-κB and Bcl-xL Independently of PI3K signaling, Cancer research, Vol. 71, No. 7, pp. 2739-2749, 2011.
[70] R. Ata, C. N. Antonescu, Integrins and cell metabolism: an intimate relationship impacting cancer, International journal of molecular sciences, Vol. 18, No. 1, pp. 189, 2017.
[71] A. K. Simi, M.-F. Pang, C. M. Nelson, Extracellular matrix stiffness exists in a feedback loop that drives tumor progression, Biomechanics in Oncology, pp. 57-67, 2018.
[72] A. N. Gargalionis, K. A. Papavassiliou, A. G. Papavassiliou, Targeting the YAP/TAZ mechanotransducers in solid tumour therapeutics, Journal of Cellular and Molecular Medicine, Vol. 27, No. 13, pp. 1911, 2023.
[73] S. A. Mosaddad, Y. Salari, S. Amookhteh, R. S. Soufdoost, A. Seifalian, S. Bonakdar, F. Safaeinejad, M. M. Moghaddam, H. Tebyanian, Response to mechanical cues by interplay of YAP/TAZ transcription factors and key mechanical checkpoints of the cell: a comprehensive review, Cell Physiol Biochem, Vol. 55, No. 1, pp. 33-60, 2021.
[74] G. Rubí-Sans, A. Nyga, M. A. Mateos-Timoneda, E. Engel, Substrate stiffness-dependent activation of Hippo pathway in cancer associated fibroblasts, Biomaterials Advances, Vol. 166, pp. 214061, 2025.
[75] C. W. Molter, E. F. Muszynski, Y. Tao, T. Trivedi, A. Clouvel, A. J. Ehrlicher, Prostate cancer cells of increasing metastatic potential exhibit diverse contractile forces, cell stiffness, and motility in a microenvironment stiffness-dependent manner, Frontiers in Cell and Developmental Biology, Vol. 10, pp. 932510, 2022.
[76] H. Y. Murad, H. Yu, D. Luo, E. P. Bortz, G. M. Halliburton, A. B. Sholl, D. B. Khismatullin, Mechanochemical disruption suppresses metastatic phenotype and pushes prostate cancer cells toward apoptosis, Molecular Cancer Research, Vol. 17, No. 5, pp. 1087-1101, 2019.
[77] W. Pan, Z. Zhang, H. Kimball, F. Qu, K. Berlind, K. H. Stopsack, G.-S. M. Lee, T. K. Choueiri, P. W. Kantoff, Abiraterone acetate induces CREB1 phosphorylation and enhances the function of the CBP-p300 complex, leading to resistance in prostate cancer cells, Clinical Cancer Research, Vol. 27, No. 7, pp. 2087-2099, 2021.
[78] M. P. Edlind, A. C. Hsieh, PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance, Asian journal of andrology, Vol. 16, No. 3, pp. 378-386, 2014.
[79] J. B. Wu, L. W. Chung, The PI3K-mTOR Pathway in Prostate Cancer: Biological Significance and Therapeutic Opportunities, PI3K-mTOR in Cancer and Cancer Therapy, pp. 263-289, 2016.
[80] R. Wang, Z. Qu, Y. Lv, L. Yao, Y. Qian, X. Zhang, L. Xiang, Important Roles of PI3K/AKT Signaling Pathway and Relevant Inhibitors in Prostate Cancer Progression, Cancer Medicine, Vol. 13, No. 21, pp. e70354, 2024.
[81] S. Heller, T. Sugawara, E. Nevedomskaya, S. J. Baumgart, H. Nguyen, E. Corey, A. Böhme, O. von Ahsen, O. Politz, B. Haendler, Abstract B065: Combining the androgen receptor inhibitor darolutamide with PI3K/AKT/mTOR pathway inhibitors has superior efficacy in preclinical models of prostate cancer, Cancer Research, Vol. 83, No. 11_Supplement, pp. B065-B065, 2023.
[82] S. Li, F. La Manna, P. Chouvardas, G. Thalmann, M. Kruithof-de Julio, Abstract B007: New generation mTOR blocker sensitizes prostate cancer models to AR-targeting therapy, Cancer Research, Vol. 83, No. 11_Supplement, pp. B007-B007, 2023.
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Volume 56, Issue 4
October 2025Pages 863-881
- Receive Date: 09 January 2025
- Revise Date: 08 February 2025
- Accept Date: 10 February 2025