Related Experiment Video
Updated: May 24, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
The quest to define cancer-specific systems parameters for personalized dosing in oncology
Areti-Maria Vasilogianni1, Brahim Achour1,2, Zubida M Al-Majdoub1
1Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK.
Introduction:
Clinical trials in oncology initially recruit heterogeneous populations, without catering for all types of variability. The target cohort is often not representative, leading to variability in pharmacokinetics (PK). To address enrollment challenges in clinical trials, physiologically based pharmacokinetic models (PBPK) models can be used as a guide in the absence of large clinical studies. These models require patient-specific systems data relevant to the handling of drugs in the body for each type of cancer, which are scarce.
Areas Covered:
This review explores system parameters affecting PK in cancer and highlights important gaps in data. Changes in drug-metabolizing enzymes (DMEs) and transporters have not been fully investigated in cancer. Their impaired expression can significantly affect capacity for drug elimination. Finally, the use of PBPK modeling for precision dosing in oncology is highlighted. Google Scholar and PubMed were mainly used for literature search, without date restriction.
Expert Opinion:
Model-informed precision dosing is useful for dosing in sub-groups of cancer patients, which might not have been included in clinical trials. Systems parameters are not fully characterized in cancer cohorts, which are required in PBPK models. Generation of such data and application of cancer models in clinical practice should be encouraged.
Insights
Physiologically based pharmacokinetic (PBPK) models can guide precision dosing in oncology for diverse patient groups. However, scarce patient-specific data and uncharacterized cancer system parameters limit their clinical application.
Area of Science:
- Pharmacology
- Oncology
- Systems Biology
Background:
- Clinical trials in oncology often enroll heterogeneous populations, leading to variability in pharmacokinetics (PK).
- Patient-specific data for physiologically based pharmacokinetic (PBPK) models in cancer are scarce, hindering trial enrollment and precision dosing.
- Variability in drug-metabolizing enzymes and transporters in cancer significantly impacts drug elimination capacity.
Purpose of the Study:
- To review system parameters influencing PK in cancer patients.
- To identify critical data gaps for PBPK model development in oncology.
- To highlight the potential of PBPK modeling for precision dosing in cancer.
Main Methods:
- Literature search using Google Scholar and PubMed without date restrictions.
- Review of system parameters affecting drug pharmacokinetics in cancer.
- Exploration of physiologically based pharmacokinetic (PBPK) modeling applications.
Main Results:
- Significant data gaps exist regarding system parameters affecting PK in cancer cohorts.
- Changes in drug-metabolizing enzymes and transporters in cancer are not fully investigated.
- PBPK models require comprehensive patient-specific data for accurate cancer drug dosing.
Conclusions:
- PBPK modeling offers a pathway for model-informed precision dosing in oncology, especially for underrepresented patient subgroups.
- Characterization of cancer-specific system parameters is crucial for advancing PBPK model utility.
- Encouraging data generation and clinical application of cancer PBPK models is recommended.
More Related Videos
06:20Irradiator Commissioning and Dosimetry for Assessment of LQ α and β Parameters, Radiation Dosing Schema, and in vivo Dose Deposition
Published on: March 11, 2021
10:03Physiologic Patient Derived 3D Spheroids for Anti-neoplastic Drug Screening to Target Cancer Stem Cells
Published on: July 5, 2019
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:27Tumor Immunotherapy
01:21Cancer Survival Analysis
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
02:18Cancer