Computational Molecular Biology 2025, Vol.15, No.3, 131-140 http://bioscipublisher.com/index.php/cmb 132 support of omics technology. It is like a searchlight, helping researchers find those key points in the vast amount of molecular information. This article mainly aims to discuss how to use multi-omics data to identify genomic markers of drug sensitivity, and also incidentally sort out the common research ideas and progress at present. Overall, it is divided into several parts. First, let's clarify what drug sensitivity is and what the molecular mechanisms behind it are roughly like. Then, let's talk about the role of genomic markers in predicting drug responses and how pharmacogenomics has developed in recent years. Next, we will turn to the transcriptome, proteome, and metabolome levels to see what value they can provide when studying drug responses and how multi-omics data can be integrated and analyzed. The last part does not offer a summary but rather a outlook, discussing the potential of artificial intelligence in predicting drug responses in the future, how omics and clinical data can be better combined, and the inspirations these studies can bring to precision medicine and new drug development. 2 Theoretical Basis of Drug Sensitivity and Genomic Markers 2.1 Definition and molecular mechanism overview of drug sensitivity Drug sensitivity, in essence, is about how strongly an organism or cell reacts to a certain drug concentration. Some people calculate it using the half-maximal inhibitory concentration (IC50), while others look at the area of the dose-response curve (AUC). Clinically, it is more intuitive, such as how much the tumor has shrunk and how long it has been since the patient relapsed. There are too many links that can affect it, from how the drug enters the cell to whether it can smoothly act on the target site after entering, all of which may go wrong. For instance, if the transporter or metabolic enzyme is inefficient, the drug cannot get in. Once the target gene mutates, the efficacy of the drug may be immediately reduced. What's even more troublesome is that tumor cells can "start anew", such as opening up backup signaling pathways or repairing damaged DNA more quickly. Some simply pump the drug out (like the exudation protein P-gp), or simply change their "personality" and undergo epithelial-mesenchymal transition (EMT), becoming insensitive to several drugs. Overall, drug sensitivity is the result of the combined action of multiple genes and pathways. To fully understand it, it is necessary to rely on the integrated analysis of multiple omics. 2.2 The role of genomic markers in drug response prediction Some patients respond particularly well to medication, while others show almost no reaction. Such differences often need to be answered in genes. Genomic markers, in essence, are genetic characteristics that can predict a person's response to a certain drug, such as gene mutations, copy number changes, different expression levels, or single nucleotide polymorphisms. If doctors know this information before treatment, they can roughly determine who is more likely to be sensitive to the drug and who may be resistant to it, thus avoiding detours (Wang et al., 2008). There are many such cases in clinical practice - for instance, in patients with non-small cell lung cancer, those with EGFR-sensitive mutations usually respond well to tyrosine kinase inhibitors (gefitinib, erlotinib). However, if KRAS mutations occur in the tumor, such drugs are basically of no use (Martin et al., 2013). Genetic mutations not only help doctors select the right drugs but also make the development of new drugs more precise. Nowadays, many clinical trials screen patients in advance, selecting those who are more likely to respond (also known as the enrichment strategy), which leads to a higher success rate. Overall, identifying and verifying these genomic markers is the most crucial step for the implementation of precision medicine. 2.3 Development and application of pharmacogenomics The discipline of pharmacogenomics was actually originally intended to figure out why the same drug has such different effects on different people. Later, research became increasingly detailed, evolving from initially focusing on individual genes to later being able to search for clues throughout the entire genome. Over the past two decades or so, scientists have discovered many genetic markers related to drug efficacy or side effects, and some of them have truly been incorporated into the hospital medication process. For instance, when it comes to the antithrombotic drug clopidogrel, before prescriming the medication, doctors will check the patient's CYP2C19 genotype. For those with weak metabolic capacity, they either adjust the dosage or change the medication (Figure 1) (Angulo-Aguado et al., 2021). There are more and more such examples, which also provide doctors with
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