Challenges in the modelling of the pharmacokinetics and pharmacodynamics of an anti-cancer drug combination on urinary bladder cancer T24 cells: a technical review

Authors

  • Suhad Hussein Atshan
  • Hussam W. Al-Humadi

DOI:

https://doi.org/10.60988/p.v37i2S.273

Keywords:

transitional cell carcinoma of the bladder; T24 cell line; in vitro pharmacokinetics / pharmacodynamics model; drug combination; chemotherapy

Abstract

The development of novel anticancer therapies requires rigorous preclinical evaluation in order to ensure both efficacy and safety prior to clinical translation. The T24 cell line, derived from human transitional bladder carcinoma, is a widely employed in vitro model owing to its aggressive phenotype and strong relevance to human disease pathology. It offers a valuable platform for investigating bladder cancer progression, drug responsiveness, and mechanisms of resistance. However, replicating the complex tumour microenvironment and accurately predicting in vivo therapeutic outcomes still pose significant challenges in vitro. The pharmacokinetics (PK) and pharmacodynamics (PD) of candidate agents must be carefully assessed, as these parameters often diverge markedly between in vitro and in vivo contexts. In vitro PK/PD modelling – linking drug concentration to biological effect – facilitates dose optimization, particularly when integrated with pulsatile drug administration and advanced methodologies that simulate the three-dimensional tumour microenvironment. Such approaches enhance the translational relevance of bladder cancer research and may improve therapeutic outcomes. This review underscores the critical importance of optimizing the experimental design of in vitro PK/PD models in an attempt to address prevailing limitations and advance bladder cancer therapy.

Author Biographies

Suhad Hussein Atshan

College of Pharmacy, University of Babylon, Hillah, Iraq
Department of Pharmacology, College of Medicine, University of Babylon, Hillah, Iraq

Hussam W. Al-Humadi

College of Pharmacy, University of Babylon, Hillah, Iraq

References

1. Pinto-Leite R., Botelho P., Ribeiro E., Oliveira P.A., Santos L. Effect of sirolimus on urinary bladder cancer T24 cell line. J. Exp. Clin. Cancer Res. 28(1), 3, 2009. DOI: 10.1186/1756-9966-28-3

2. Barbosa M.A.G., Xavier C.P.R., Pereira R.F., Petrikaitė V., Vasconcelos M.H. 3D cell culture models as recapitulators of the tumor microenvironment for the screening of anti-cancer drugs. Cancers (Basel) 14(1), 190, 2021. DOI: 10.3390/cancers14010190

3. Habanjar O., Diab-Assaf M., Caldefie-Chezet F., Delort L. 3D cell culture systems: tumor application, advantages, and disadvantages. Int. J. Mol. Sci. 22(22), 12200, 2021. DOI: 10.3390/ijms222212200

4. Jihad S., Al-Saigh R.J., Al-Humadi H.W. The impact of human albumin on the activity of some anti-staphylococcal agents in an in vitro pharmacokinetics / pharmacodynamics model. Rev. Clin. Pharmacol. Pharmacokinet. Int. Ed. 38(s2), 129–132, 2024. DOI: 10.61873/ILCP1133

5. Caramelo B., Zagorac S., Corral S., Marqués M., Real F.X. Cancer-associated fibroblasts in bladder cancer: origin, biology, and therapeutic opportunities. Eur. Urol. Oncol. 6(4), 366–375, 2023. DOI: 10.1016/j.euo.2023.02.011

6. Abdalwahd N., Al-Saigh R.J., Al-Humadi H.W. Assessment of antifungal drugs’ activity against some Candida albicans isolates in the presence or absence of human albumin: a study employing an in vitro pharmacokinetics / pharmacodynamics model. Rev. Clin. Pharmacol. Pharmacokinet. Int. Ed. 38(s2), 39–42, 2024. DOI: 10.61873/SEXH5182

7. Urzì O., Gasparro R., Costanzo E., De Luca A., Giavaresi G., Fontana S., et al. Three-dimensional cell cultures: the bridge between in vitro and in vivo models. Int. J. Mol. Sci. 24(15), 12046, 2023. DOI: 10.3390/ijms241512046

8. Warrick J.I., Sjödahl G., Kaag M., Raman J.D., Merrill S., Shuman L., et al. Intratumoral heterogeneity of bladder cancer by molecular subtypes and histologic variants. Eur. Urol. 75(1), 18–22, 2019. DOI: 10.1016/j.eururo.2018.09.003

9. Bouhaddou M., Yu L.J., Lunardi S., Stamatelos S.K., Mack F., Gallo J.M., et al. Predicting in vivo efficacy from in vitro data: quantitative systems pharmacology modeling for an epigenetic modifier drug in cancer. Clin. Transl. Sci. 13(2), 419–429, 2020. DOI: 10.1111/cts.12727

10. Khan S.U., Fatima K., Aisha S., Malik F. Unveiling the mechanisms and challenges of cancer drug resistance. Cell Commun. Signal. 22(1), 109, 2024. DOI: 10.1186/s12964-023-01302-1

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Published

10-10-2025

How to Cite

[1]
Atshan, S.H. and Al-Humadi, H.W. 2025. Challenges in the modelling of the pharmacokinetics and pharmacodynamics of an anti-cancer drug combination on urinary bladder cancer T24 cells: a technical review. Pharmakeftiki . 37, 2S (Oct. 2025). DOI:https://doi.org/10.60988/p.v37i2S.273.