Pharmacogenomics — the study of how genes influence drug responses — is a cornerstone of personalised medicine. Patients often respond differently to the same therapy, experiencing variations in efficacy, tolerance, or adverse effects. Understanding this variability requires models that can replicate aspects of human genetic diversity, metabolic capacity, and cellular signalling. Immortalised cell lines provide the reproducible platforms necessary for investigating drug response variability. By serving as surrogates for specific tissues, they allow researchers to explore how genetic mutations, metabolic pathways, or receptor differences influence treatment outcomes. The following sections examine ten widely used cell lines and their role in advancing pharmacogenomics.
HeLa Cells and Chemotherapy Variability
HeLa cells have long been used to investigate variability in chemotherapy responses. As cervical carcinoma-derived cells with a highly mutated genome, they exemplify how genetic instability influences drug sensitivity. HeLa systems contribute to pharmacogenomic research by:
- Screening anticancer drugs, showing how tumour mutations affect treatment efficacy.
- Investigating DNA repair pathways, which underlie resistance to radiation and chemotherapy.
- Identifying biomarkers, helping predict patient outcomes based on genetic alterations.
Although HeLa cannot represent all patients, their historical and ongoing use highlights the importance of genetic variation in shaping drug responses.
HEK293 and Receptor Pharmacogenomics
HEK293 cells are uniquely suited for pharmacogenomics because of their high transfection efficiency. Researchers can introduce patient-specific genetic variants into HEK293 to study how altered receptors or transporters affect drug binding and signalling. Applications include:
- Pharmacogenomic receptor studies, modelling mutations in G-protein coupled receptors or ion channels.
- Drug–gene interaction testing, exploring how genetic polymorphisms alter pharmacodynamics.
- Gene editing validation, using CRISPR-modified HEK293 lines to mimic patient-specific genotypes.
By linking genetic variation to receptor function, HEK293 systems provide clarity on why drugs work differently across populations.
CHO Cells and Biologic Drug Optimisation
While CHO cells are widely recognised for biomanufacturing, they also play a role in pharmacogenomics by producing customised biologics. Variations in glycosylation patterns can significantly affect drug efficacy and safety, making CHO cells vital for adjusting therapies to patient-specific needs. In drug response variability studies, CHO cells are used to:
- Engineer biologics with altered half-lives, tailored to metabolic profiles.
- Study glycosylation variants, which influence immune recognition and clearance.
- Produce monoclonal antibodies, optimised for patient-specific tumour antigens.
This adaptability ensures CHO cells remain central to pharmacogenomic approaches for biologic therapies.
SH-SY5Y and Neurological Drug Sensitivity
Neuropharmacogenomics — the study of genetic influences on neurological drug responses — relies heavily on neuronal models such as SH-SY5Y. These neuroblastoma-derived cells can differentiate into neuron-like phenotypes, making them ideal for studying patient-specific variations in neurotransmitter systems. They are applied to:
- Antidepressant response variability, linked to serotonin transporter gene polymorphisms.
- Antipsychotic drug sensitivity, influenced by dopamine receptor genetic variants.
- Neurotoxic drug reactions, revealing genetic risk factors for neurological side effects.
SH-SY5Y helps clarify why psychiatric and neurological treatments produce highly variable outcomes among individuals.
MCF7 and Hormone Therapy Responses
The MCF7 breast cancer line demonstrates how pharmacogenomics applies to endocrine therapies. Since MCF7 retains oestrogen receptor activity, it is widely used to model genetic and molecular determinants of drug response in hormone-sensitive cancers. Research with MCF7 has highlighted:
- Variability in tamoxifen sensitivity, linked to CYP2D6 polymorphisms that alter drug metabolism.
- Mechanisms of resistance, showing how genetic mutations enable tumours to bypass hormone blockade.
- Predictive biomarkers, guiding personalised endocrine therapy regimens.
By replicating hormone-driven cancer pathways, MCF7 underscores the importance of pharmacogenomics in oncology.
THP1 and Immune Response Diversity
The THP1 monocytic line plays a vital role in studying pharmacogenomics of the immune system. Because patients often respond differently to immunomodulatory drugs, THP1 systems allow exploration of genetic influences on innate immune responses. They are used to:
- Test cytokine release variability, where genetic differences influence immune activation.
- Evaluate immunotoxicity, predicting which individuals may experience adverse immune responses.
- Explore host–drug interactions, clarifying variability in immune responses to biologics.
THP1-based pharmacogenomics bridges immune diversity with drug safety, ensuring immunotherapies are tailored to patient populations.
A2780 and Resistance to Chemotherapy
Drug resistance is a major focus of pharmacogenomics, and A2780 ovarian carcinoma cells are central to this work. Their sensitivity to platinum-based drugs provides a baseline for exploring resistance mechanisms that emerge in patient tumours. Through A2780 pharmacogenomic studies, researchers have:
- Identified resistance-associated genes, such as those in DNA repair pathways.
- Explored efflux transporter variability, which alters intracellular drug accumulation.
- Tested predictive biomarkers, guiding therapy selection for ovarian cancer patients.
A2780 demonstrates how pharmacogenomics helps clinicians anticipate drug resistance and personalise chemotherapy.
HL-60 and Haematological Drug Responses
The promyelocytic HL-60 line provides a model for pharmacogenomics in blood cancers. Their ability to differentiate into granulocytes or monocytes allows for testing how genetic variation affects haematological drug responses. Applications include:
- Variability in differentiation therapy, particularly with retinoic acid analogues.
- Chemotherapy toxicity studies, revealing patient-specific risk of haematopoietic suppression.
- Targeted therapy optimisation, modelling genetic subtypes of acute myeloid leukaemia.
HL-60 helps link genetic variation to drug outcomes in haematology, supporting precision treatment of leukaemia.
Caco-2 and Pharmacokinetic Variability
Absorption variability is a central concern in pharmacogenomics, and Caco-2 cells are essential for investigating this phenomenon. By differentiating into enterocyte-like cells, they simulate intestinal absorption, where genetic differences in transporters and enzymes can affect drug bioavailability. They are widely used to:
- Study efflux transporter polymorphisms, such as P-glycoprotein variants influencing drug absorption.
- Test nutrient–drug interactions, showing how diet and genetics combine to affect uptake.
- Model variability in oral bioavailability, predicting which patients may require dosage adjustments.
Caco-2 pharmacogenomics underscores the role of absorption in drug response variability, guiding dosing strategies in precision medicine.
HepG2 and Pharmacogenomic Metabolism
As the liver is the primary site of drug metabolism, HepG2 cells are indispensable for pharmacogenomics. Derived from hepatocellular carcinoma, they retain many metabolic pathways, allowing exploration of how genetic differences alter drug clearance and toxicity. HepG2 systems are used to:
- Test cytochrome P450 polymorphisms, which strongly influence drug metabolism.
- Predict hepatotoxicity, clarifying which patients may be genetically predisposed to liver injury.
- Explore drug–drug interactions, relevant to patients on complex therapeutic regimens.
By linking genetic variability with hepatic metabolism, HepG2 helps guide dosing strategies that reduce risk and improve efficacy.
Conclusion
Pharmacogenomics is reshaping medicine by revealing how genetic diversity influences drug responses. Immortalised cell lines serve as critical models in this pursuit, offering reproducible systems for investigating variability in drug efficacy, toxicity, and metabolism. HeLa highlights tumour heterogeneity, HEK293 clarifies receptor pharmacogenomics, and CHO enables customised biologics. SH-SY5Y supports neurological drug response studies, MCF7 advances hormone therapy precision, and THP1 illuminates immune variability. A2780 clarifies chemotherapy resistance, HL-60 supports precision haematology, Caco-2 models absorption variability, and HepG2 reveals metabolic diversity. Together, these models underpin the translation of pharmacogenomic insights into clinical practice. By enabling targeted therapies, optimised dosing, and reduced adverse effects, they help bring the promise of personalised medicine closer to reality.