The individual differences in drug therapy have always been a concern in medical research and clinical practice. Under the same treatment conditions, there may be significant differences in the response of different individuals to drugs. This not only affects the therapeutic effect, but may also lead to adverse reactions and drug toxicity. One of the fundamental reasons for this individual difference is genetic variation. With the completion of the Human Genome Project and the development of high-throughput sequencing technology, people have gained a deeper understanding of the association between genes and drug responses.

Drug toxicity, as a major side effect of drug therapy, involves multiple mechanisms, including drug metabolism, transport, target selectivity, and immune system response. In previous studies, it has been found that the toxic reactions caused by different drugs may have similar manifestations, but their underlying mechanisms are different. Therefore, it is of great significance for people to deeply explore the types and mechanisms of drug toxicity, understand the pathways of drug action in the body, avoid or reduce the occurrence of drug toxicity, and develop more personalized treatment plans for patients (Li et al., 2021).

In the process of drug therapy, drug metabolism and transport are key factors affecting drug concentration and efficacy. In this context, mutations in specific genes can directly affect the metabolic rate, clearance rate, and sensitivity of drugs. Key genes such as the CYP family and transporter family play crucial roles in drug metabolism pathways. People's in-depth study of the functions and variations of these genes is of great clinical significance in predicting the metabolic efficiency of individuals towards specific drugs, thereby providing more accurate guidance for personalized medication (Fu et al., 2021).

In clinical practice, personalized therapy has achieved significant results in some fields. Targeted drugs and immunotherapy in cancer treatment are one of the successful cases of personalized therapy. This study provides a comprehensive review of the types and mechanisms of toxic reactions caused by different drugs, delves into the relationship between specific genetic variations and drug metabolism, analyzes the application of personalized therapy in clinical practice, and aims to reveal the precise relationship between individual genotypes and drug effects, providing more accurate guidance for personalized medication.

1 Types and Mechanisms of Drug Toxicity

1.1 Hepatotoxicity

The liver, as one of the largest internal organs in the human body, has critical physiological functions, including drug metabolism and detoxification. However, it is precisely due to its complex and efficient metabolic mechanisms that the liver has become one of the main target organs for many drug induced adverse reactions. Hepatotoxicity refers to the damage caused by drugs or other chemicals to the structure and function of liver tissue, which involves multiple complex molecular and cellular level reactions (Figure 1).

Figure 1 Depiction of factors responsible for causing hepatotoxicity upon doxorubicin treatment (Prasanna et al., 2020)

This toxicity mechanism involves multiple aspects, including oxidative metabolism and the generation of toxic intermediate metabolites. In the liver, the cytochrome P450 enzyme family mediates the oxidative metabolism of many drugs, and the intermediate metabolites produced may directly damage liver cells. In addition, reactive metabolites generated during drug metabolism may bind to proteins in the liver, forming antigenic complexes that trigger immune responses, leading to damage to liver cells. The disruption of redox balance is also one of the mechanisms leading to hepatotoxicity. Drugs may interfere with redox balance, causing excessive generation of oxygen free radicals or reactive oxygen species, and causing damage to cell structure and function (Ma et al., 2023).

Hepatotoxicity also involves complex mechanisms in multiple aspects such as cell apoptosis and necrosis, bile stasis, and immune response. These processes are intertwined to form a complex network, understanding these mechanisms is important for predicting and alleviating the adverse effects of drugs on the liver, as well as developing safer drug treatment plans.

1.2 Cardiovascular toxicity

Cardiovascular toxicity refers to the damage caused by drugs or other chemicals to the structure and function of the cardiovascular system, which may involve the heart, blood vessels, and other related tissues. The mechanisms of cardiovascular toxicity are diverse, including direct damage to cardiac cells, impact on electrophysiological processes, leading to vascular damage, and affecting cardiac contractile function. These adverse effects may lead to abnormalities in the structure and function of the cardiovascular system through multiple pathways.

Some antibiotics, especially aminoglycosides and quinolones, have been found to be associated with cardiovascular toxicity. This includes some antibiotics that may cause arrhythmia, such as quinine and azithromycin. At the same time, some anti-cancer drugs are also believed to have toxic effects on the heart, such as Xinde Bao and Doxorubicin, which may cause myocardial damage and even lead to heart failure (Zaki et al., 2022).

In this regard, the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is also associated with adverse effects on the cardiovascular system. NSAIDs may increase the risk of hypertension, heart attack, and stroke. Among antipsychotic drugs, some specific antipsychotic drugs may be associated with cardiovascular toxicity, causing arrhythmias, cardiovascular events, and other cardiovascular problems. In addition, the abuse of stimulants, especially some illegal drugs or excessive use of prescription drugs such as cocaine and methamphetamine (methamphetamine), may have direct toxic effects on the cardiovascular system, leading to hypertension, arrhythmia, and myocardial infarction.

1.3 Immune system toxicity

Immune system toxicity refers to the adverse effects of drugs or other chemicals on the immune system, which may include allergic reactions, immune-mediated hepatitis, increased risk of infection caused by immunosuppressive drugs, and potential autoimmune diseases caused by certain drugs. The mechanisms of immune system toxicity are diverse and may involve direct interaction between drugs and immune cells, affecting their function. Meanwhile, there are complex interactions between the immune system and drug metabolism, and some drugs may affect drug metabolism by affecting the activity of immune cells, leading to immune system toxicity.

Drugs may trigger excessive activation of the immune system, leading to abnormal immune responses. In this case, the immune system may produce allergic reactions to drugs, with the mechanism mediated by immunoglobulin E (IgE) playing a crucial role. This allergic reaction triggers the release of histamine and other inflammatory mediators, leading to a series of reactions of varying degrees, ranging from mild rash to severe allergic shock. Certain drugs may lead to immune-mediated hepatitis, a response caused by the immune system's attack on liver tissue, manifested as elevated liver enzyme levels, jaundice, and other symptoms (Zhang et al., 2020).

Immunosuppressive drugs are commonly used to prevent organ transplant rejection or treat autoimmune diseases, but such drugs may weaken normal immune responses and increase the risk of infection. Therefore, doctors need to carefully balance the relationship between treatment effectiveness and infection risk when using such drugs. In addition, some drugs may induce autoimmune diseases, where the immune system mistakenly attacks the body's tissues and is associated with the occurrence of autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis.

2 The Relationship between Genetic Variation and Drug Metabolism

2.1 The impact of CYP family gene mutations

The cytochrome P450 family (CYP family) is a gene family that encodes important drug metabolism enzymes in the liver, playing a crucial role in drug metabolism. Genetic variation refers to the genetic variation of CYP genes in the human body, which may have a significant impact on drug metabolism and individual response to drugs. This genetic variation is an important source of individual differences, which can lead to different metabolic rates of drugs in the body, thereby affecting the efficacy and adverse reactions of drugs.

The variation of CYP family genes is mainly manifested in differences in genotype and allele frequencies. The differences between different genotypes may lead to differences in drug metabolism ability, which in turn affects the concentration of drugs in the body. This difference is widely studied in clinical practice because it has significant implications for the metabolism and response of individuals to certain drugs. The variation of some CYP genes has been confirmed to be associated with a decrease or increase in drug metabolism enzyme activity, thereby affecting the clearance rate of drugs in the body. The most prominent impact is on genes such as CYP2D6, CYP2C9, and CYP2C19. For example, mutations in the CYP2D6 gene are associated with various drug metabolism, including antidepressants β Receptor antagonists and antiarrhythmic drugs, etc. The variation of the CYP2C9 gene affects the metabolism of anticoagulants such as warfarin, which may increase the risk of bleeding or thrombosis (Wang, 2023).

The impact of these genetic variations is also reflected in the pharmacokinetics and pharmacodynamics of drugs, namely the changes in the absorption, distribution, metabolism, and excretion processes of drugs in the body, as well as the effects of drugs on targets.

2.2 The role of transporter gene mutations

The variation of transporter genes plays a crucial role in drug metabolism and transportation, and has a significant impact on individuals, drug responses, and the effectiveness of drug therapy. Transporters are proteins responsible for regulating the absorption, distribution, and excretion of drugs in the body, and their function and expression levels are regulated by genetic variations. These genetic variations involve multiple transporters, including the ABC family, SLC family, etc. This mutation may lead to changes in the structure and function of transporters, affecting the drug transport process and causing varying degrees of drug concentration changes in the body, thereby affecting individual responses to drugs.

The variation of ABCB1 (P-gp) gene is a research focus in the ABC family. P-gp (P-glycoprotein) is a transporter protein located on the cell membrane, involved in the drug export process. The polymorphism of ABCB1 gene may lead to changes in the expression level and activity of P-gp, thereby affecting the transport and clearance speed of multiple drugs in vivo. This has significant clinical significance in drug metabolism and resistance, especially for the use of various anti-cancer drugs in cancer treatment.

In addition, genetic variations in the SLC family also play an important role in drug metabolism and transport. The SLC family includes various transporters related to drug absorption and distribution, such as OATP, OCT, and MATE. Variiation in these genes may lead to the alteration of drug absorption and distribution in the body, which in turn affects the drug pharmacokinetics (Li et al., 2022).

2.3 Comprehensive analysis of genetic variation and drug effects

The relationship between genetic variation and drug effects is one of the core issues in the fields of personalized medicine and precision drug therapy. Genetic variation, as an important manifestation of individual genetic information, has a profound impact on drug metabolism, drug target binding, drug absorption, distribution, and excretion.

The variation of CYP family genes is a significant example. The enzymes encoded by the CYP gene play a crucial role in drug metabolism pathways, and genetic variations may lead to a decrease or increase in the activity of drug metabolism enzymes, thereby affecting the speed of drug clearance in the body. This mutation causes significant differences in individual metabolism and response to drugs, for example, mutations in genes such as CYP2D6, CYP2C9, and CYP2C19 are closely related to the efficacy and adverse reactions of antidepressants, anticoagulants, and other drugs.

The variation of transporter genes also plays a crucial role in regulating the absorption and distribution of drugs in the body. For example, mutations in the ABC family genes, especially the ABCB1 gene, are closely related to the pharmacokinetics and pharmacodynamics of multiple drugs. This mutation may lead to changes in the drug's transport process in the body, thereby affecting the efficacy and safety of the drug. In addition, genetic variations in the SLC family are also related to drug absorption and distribution, for example, variations in the OATP1B1 gene are associated with the metabolism and tolerance of statins.

Genetic variation has multiple impacts on an individual's sensitivity and response to drugs. In some cases, genetic mutations may lead to a decrease in the clearance rate of drugs in the body, increasing drug exposure and potentially increasing the risk of adverse reactions. In other cases, genetic mutations may lead to rapid drug metabolism, weakening the efficacy of the drug.

3 Clinical Significance and Personalized Therapy

3.1 Genetic markers of individual response to specific drugs

The genetic markers of individual responses to specific drugs are key elements of personalized medicine, revealing the close relationship between genes and drug metabolism, pharmacology, and adverse drug reactions. These genetic markers play a crucial role in the individual's response to drugs, profoundly influencing the effectiveness and safety of drug therapy.

The enzymes encoded by the CYP family play a core role in drug metabolism pathways, and variations in gene markers may lead to an increase or decrease in drug metabolism enzyme activity, thereby affecting the speed of drug clearance. For example, the labeling of genes such as CYP2D6, CYP2C9, and CYP2C19 is closely related to the efficacy and adverse reactions of various drugs. Individuals can be classified into different types of drug metabolism based on their genotype, such as those with high metabolism, normal metabolism, or slow metabolism, which helps predict differences in patient response to specific drugs.

In addition to gene markers of drug metabolism enzymes, transporter gene markers are also important factors affecting an individual's drug response. The ABCB1 (P-gp) gene marker in the ABC family, as well as markers in the SLC family, such as OATP1B1, are involved in drug absorption, distribution, and excretion. The variation of these genetic markers may lead to changes in the structure or function of transport proteins, thereby affecting the drug transport process in vivo (Mikko et al., 2021).

3.2 Clinical success cases of personalized therapy

Personalized therapy has achieved a series of exciting success cases in clinical practice. The successful cases of personalized therapy highlight the crucial role of a deep understanding of the complex relationship between genes and drugs in medical progress. By delving deeper into the genetic information of patients, the medical community can more accurately select the treatment plan that best suits the individual characteristics of patients.

By gaining a deeper understanding of the patient's tumor genotype, doctors can develop more precise treatment plans, thereby improving the targeting and efficacy of treatment. In clinical practice, some cancer patients with specific gene mutations have benefited from personalized therapy. For example, HER2 positive breast cancer patients have achieved significant survival advantages by using anti HER2 targeted drugs, such as Herceptin and Trastuzumab (Li et al., 2022). Similarly, non-small cell lung cancer patients with positive EGFR mutations exhibit excellent therapeutic responses to EGFR inhibitors such as gefitinib and ecytinib (Liu et al., 2022).

Another successful case is immunotherapy in the field of leukemia. CAR-T cell therapy is an personalized therapy method that involves obtaining the patient's own T cells, genetically modifying them to have stronger anti-tumor ability, and then re implanting them into the patient's body (Shunsuke et al., 2021). This treatment method has shown astonishing efficacy in some leukemia patients, enabling some patients with advanced diseases that are difficult to cure to achieve long-term remission (Figure 2).

Figure 2 Trafficking and infiltration of tumors (Sterner and Sterner, 2021)

3.3 The feasibility and challenges of genetic testing

Genetic testing, as an advanced medical technology, has broad feasibility. With the rapid development of genetic testing technology, its cost is gradually decreasing and efficiency is constantly improving, making it affordable and beneficial for more patients to access individual genetic information. This provides strong support for personalized healthcare, enabling doctors to better understand the patient's genetic background and develop more precise treatment plans. The feasibility of genetic testing is also reflected in its potential applications for prevention and early screening, helping people better understand their own disease risks and adopt more targeted health management measures.

However, genetic testing faces a series of challenges. Ethical and privacy issues are important considerations in the field of genetic testing. The sensitivity of individual genetic information means that a sound privacy protection mechanism needs to be established to prevent the misuse or leakage of genetic data. In addition, the interpretation and communication of genetic testing results also require professional genetic counseling to ensure that the patients fully understand the test results and avoid unnecessary psychological pressure or misunderstandings.

Another challenge is the standardization and normalization of genetic testing. At present, the standardization level of genetic testing is relatively low, and different laboratories may use different testing methods and technical standards, resulting in inconsistent results. This affects the reliability and reproducibility of genetic testing results to a certain extent, and it is necessary to establish more unified quality control standards and processes to ensure that the results of genetic testing can remain consistent in different environments.

The clinical interpretation and application of genetic testing also require more in-depth research. Although there are some clear evidences of the association between genes and diseases, there are still many cases in practice where the function and clinical significance of gene mutations are unclear. This makes it possible for doctors to face uncertainties in interpreting results in practice, and more research is needed to reveal a more precise relationship between genetic variants and disease.

4 Summary and Outlook

This study reveals the fact that individual differences in drug response are closely related to genetic factors by delving into the association between drug toxicity and specific genetic variations. The types and mechanisms of drug toxicity involve multiple organ systems, including the liver, cardiovascular system, and immune system. The variation of specific genes affects drug metabolism, transport, and target interactions, providing new directions for developing effective prevention and treatment strategies.

Key genes such as the CYP family and transporter family play crucial roles in drug metabolism pathways. By delving deeper into the functions and variations of these genes, doctors can more accurately predict an individual's metabolic rate towards specific drugs. The genetic variation of the CYP family may lead to an increase or decrease in the activity of drug metabolism enzymes, thereby affecting the clearance rate of drugs in the body. Meanwhile, genetic variations in the transporter family also play a crucial role in the absorption and distribution of drugs in the body. In the study of genetic markers, the interpretation and standardization of markers is one of the main challenges currently faced, which requires further research to clarify the specific relationship between gene variation and drug effects.

Personalized therapy has achieved success in some fields, such as targeted drugs and immunotherapy in cancer treatment. By delving deeper into individual genetic information, doctors can better predict patient reactions to drugs and develop more accurate treatment plans. However, the clinical application of personalized therapy still faces ethical, privacy, and standardization issues. Future research should pay more attention to combining genetic testing with practical treatment, promoting personalized therapy to be more deeply applied in a wider range of disease fields (Shirley, 2020).

There is a close correlation between drug toxicity and specific genetic variations, and an individual's genotype directly affects their metabolism and response to drugs. This provides a scientific foundation for personalized healthcare and opens up new doors for developing more personalized and precise treatment plans. Looking ahead to the future, it is foreseeable that genetic testing technology will continue to develop rapidly, with further cost reduction and improved detection efficiency and accuracy. This will promote the widespread application of genetic testing in medicine, not only in drug therapy, but also in prevention, early screening, and chronic disease management.

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