Research Report

Targeted Therapy for Specific Genetic Variations in Cancer  

Jiaren Zhou
Zhuji Central Hospital, Zhuji, 311800, China
Author    Correspondence author
International Journal of Clinical Case Reports, 2024, Vol. 14, No. 2   
Received: 29 Mar., 2024    Accepted: 30 Apr., 2024    Published: 12 May, 2024
© 2024 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Targeted therapy for specific genetic variations in cancer represents an important breakthrough in the field of modern medicine. Targeted therapy provides more effective and precise treatment methods by intervening with specific molecular targets or communication pathways in cancer cells. Especially in cancer treatment driven by specific genetic variations, targeted therapy has achieved significant success, significantly improving the survival rate and quality of life of patients. Targeted therapy emphasizes the crucial role of molecular diagnosis and biomarkers, encouraging deeper research into the molecular mechanisms of diseases in order to find new therapeutic targets. This review discusses the role of genetic variation in cancer and the principles and applications of targeted therapy. It combines relevant cases to deeply explore the importance of targeted therapy for specific genetic variations in cancer, providing profound insights for better response to cancer and improving treatment effectiveness, and promoting progress in the medical field.

Cancer; Genetic variation; Targeted therapy; Personalized medicine; Case analysis

Cancer is a disease characterized by the abnormal growth and spread of cells, which can occur in various organs and tissues of the human body. According to data from the World Health Organization, cancer is the second leading cause of death globally, causing over 9 million deaths annually. Different types of cancer exhibit distinct pathological characteristics and treatment responses, making cancer treatment highly challenging. The global epidemic trends of cancer prevalence indicate a continuous rise in incidence, posing significant health and economic burdens on affected individuals and exerting immense pressure on society and healthcare systems.


The genetic basis of cancer has always been of great concern to researchers. During the process of cancer initiation and development, gene mutations and genetic variations play crucial roles. These genetic variations can be inherited from parents or caused by environmental factors throughout life. Research on the genetic basis helps people better understand the mechanisms of cancer occurrence and provides a foundation for targeted treatments against specific genetic variations. Genetic variations refer to DNA sequences in an individual's genome that differ from the reference genome. These variations can include single nucleotide polymorphisms (SNPs), gene mutations, gene rearrangements, and so on. Genetic variations can exist widely among individuals or within populations, and they are a part of biological diversity, serving as one of the driving forces of evolution.


Targeted therapy is a cancer treatment strategy designed to intervene in specific biological processes or molecular signaling pathways within cancer cells. This treatment approach selectively disrupts the survival and proliferation of cancer cells, reducing damage to normal cells, while simultaneously enhancing the effectiveness and tolerance of the treatment (Jacob et al., 2021). The key to targeted therapy lies in accurately identifying cancer-related molecular targets and using corresponding drugs or treatment methods for intervention. The development of targeted therapy can be traced back to the late 20th century when scientists first revealed specific molecular changes in certain cancer cells. These molecular changes include gene mutations, protein overexpression, and abnormalities in signaling pathways, which have become crucial targets for targeted therapy. The advent of the first generation of targeted drugs marked a significant breakthrough in the field of cancer treatment, such as the successful use of Imatinib for treating chronic myeloid leukemia, demonstrating the feasibility of targeted therapy. Subsequently, the field of targeted therapy has experienced rapid development, continuously introducing new targeted drugs and treatment methods, providing more treatment options for cancer patients (Li et al., 2019).


This review aims to explore the importance and prospects of targeted therapy for specific genetic variations in cancer. By delving into the role of genetic variations in cancer, as well as the principles and applications of targeted therapy, a better understanding of how to improve cancer treatment in the future will be gained. This knowledge will contribute to providing more effective treatment options for patients.


1 Genetic Variations and Cancer

1.1 Common cancer-associated genetic variations

Common cancer-associated genetic variations refer to specific gene or genomic changes closely associated with the occurrence and development of cancer. These genetic variations play a crucial role in different types of cancer, profoundly influencing cancer susceptibility, growth, metastasis, and treatment responses


BRAF (v-Raf murine sarcoma viral oncogene homolog B) is a common cancer-associated gene, especially in melanoma. The V600E mutation in the BRAF gene is one of the most common genetic variations in melanoma (Figure 1). This mutation activates the MAPK signaling pathway, leading to uncontrolled proliferation of melanoma cells. Targeted drugs against the BRAF V600E mutation, such as Ipilimumab and Vemurafenib, have shown significant therapeutic effects (Goto et al., 2022).



Figure 1 V600E mutation of BRAF gene


In non-small cell lung cancer, mutations in the epidermal growth factor receptor (EGFR) significantly impact both treatment and prognosis. EGFR mutations can lead to uncontrolled cell growth and differentiation, thereby promoting the development of cancer. Drugs targeting EGFR mutations, such as Gefitinib and Erlotinib, have demonstrated significant efficacy in patients with non-small cell lung cancer.


The biological mechanisms of genetic variations refer to the biological processes and molecular mechanisms that lead to changes in genes or the genome. These variations may include single nucleotide polymorphisms, gene mutations, gene rearrangements, chromosomal abnormalities, etc. They can have a broad impact on an individual's genetic information and phenotype.


Point mutation refers to a change in one or more nucleotides in the DNA sequence, which may result in the production of a new protein, alteration of protein function, or the appearance of a stop codon. This type of mutation is common in cancer and genetic diseases. For example, base transition mutations may lead to the substitution of one amino acid for another, thereby altering the structure and function of the protein. Gene rearrangement refers to the rearrangement of two or more gene segments on a chromosome, typically playing a crucial role in the development of the immune system. In diseases such as lymphoma and leukemia, gene rearrangement can lead to new combinations of immunoglobulin genes, resulting in abnormal B cells or T cells. Chromosomal abnormalities involve changes in whole chromosomes, chromosome segments, or the number of chromosomes. For instance, Down syndrome, caused by the triplication of chromosome 21, is an example of chromosomal abnormality. Such chromosomal abnormalities can lead to various changes in physical features and cognitive functions (Block and McGronohon, 2021).


The biological mechanisms of genetic variations are complex and diverse, encompassing changes at the genomic level as well as influences on gene regulation and expression. These variations may occur naturally or be induced by environmental factors.


1.3 Personalized medicine and genetic variations

Personalized Medicine is an emerging medical approach that relies on individual genetic, molecular, and biological characteristics to guide medical decisions and treatments. Genetic variations play a crucial role in personalized medicine, as they provide healthcare professionals with individual biological information about patients. This allows for more accurate predictions of disease risk, disease diagnosis, selection of optimal treatments, and monitoring treatment effectiveness (Kiyotani et al., 2021).


Personalized medicine allows doctors to assess the risk of disease based on the patient's genetic variations. Through genetic testing, it can be determined whether a patient carries certain genetic mutations that may increase their risk of developing a hereditary disease. For example, mutations in the BRCA1 and BRCA2 genes are associated with a high risk of breast and ovarian cancers. Therefore, genetic testing can help women understand if they have these mutations, enabling them to take early preventive measures.


Personalized medicine can guide drug treatment selection based on genetic information. The effectiveness and safety of certain drugs may vary due to individual patients' genetic variations. For example, lung cancer patients with EGFR gene mutations may be more responsive to specific targeted drugs (such as Gefitinib). Therefore, doctors can choose the most appropriate treatment plan for patients based on genetic information to enhance treatment effectiveness.


Individual genetic variations can also impact the metabolism and degradation of drugs. Some individuals may have specific mutations in drug-metabolizing enzymes, resulting in either faster or slower metabolism of certain drugs. This can lead to fluctuations in drug concentrations in the body, affecting treatment effectiveness and toxicity. By understanding the patient's drug metabolism genotype, doctors can adjust drug dosages to ensure the optimal therapeutic outcome.


2 Targeted Therapy

2.1 Classification of targeted drugs

Targeted therapy is a cancer treatment approach that inhibits the growth and survival of cancer cells by interfering with specific molecular targets within these cells. These drugs attack cancer cells in a more precise manner, minimizing damage to normal cells (Figure 2). Targeted drugs can be classified into different categories based on their mechanisms of action and targets.



Figure 2 Targeted drug therapy for cancer


Tyrosine kinase inhibitors (TKIs) are a class of targeted drugs that block the growth signals of cancer cells by inhibiting the activity of receptor tyrosine kinases (Claudiani et al., 2021). They are commonly used in the treatment of solid tumors and hematologic malignancies. For example, Imatinib is used for chronic myeloid leukemia, and Gefitinib and Erlotinib are used for non-small cell lung cancer.


Antibody therapy involves the use of monoclonal antibodies to recognize and bind to specific antigens on the surface of tumor cells, thereby triggering the immune system's attack or directly blocking the growth signals of cancer cells. For example, Trastuzumab is used for the treatment of breast cancer, and Cetuximab is used for colon cancer.


Poly (ADP-ribose) polymerase (PARP) inhibitors are used to treat cancer patients with mutations in DNA repair genes such as BRCA1/2. These drugs work by inhibiting the activity of PARP enzymes, disrupting the DNA repair mechanism in cancer cells and causing cell death. Olaparib and Niraparib are common PARP inhibitors.


The classification of targeted drugs depends on their mechanisms of action and targets. The selection and application of these drugs will be determined based on the specific disease and molecular characteristics of the patient. This personalized treatment approach holds the promise of improving treatment outcomes and survival rates for cancer patients.


2.2 Mechanisms of targeted therapy

Targeted therapy is a treatment strategy used for cancer and other diseases. Its mechanism is based on intervening in specific biomolecules or signaling pathways related to the disease, aiming to inhibit or block the growth and spread of diseased cells.


Doctors and researchers need to identify specific targets in cancer cells, which are often molecules or signaling pathways closely associated with the development and growth of cancer. This can be achieved through molecular biology, genomics, proteomics, and cell biology techniques. Once the targets are identified, scientists can design and develop specific drugs that interact with these targets in different ways. These drugs are typically prepared through molecular engineering or synthetic organic chemistry methods. Targeted therapy drugs can interact with targets through different mechanisms, depending on the nature of the target. Some targeted therapy drugs not only treat cancer by inhibiting growth signals but also induce apoptosis (cell self-destruction) in cancer cells. This can be achieved by affecting DNA repair, metabolism, or the cell cycle of the cells. Immune checkpoint inhibitors are a class of targeted therapy drugs that enhance the immune system's attack on cancer cells by relieving the suppression of T cells. This treatment activates the patient's own immune system, helping it identify and destroy cancer cells (Pan and Xiong, 2022).


The mechanism of targeted therapy involves the precise identification of targets, drug design and development, and specific interactions between drugs and targets. These drugs attack disease-related biomolecules or signaling pathways in a more precise manner, offering more effective treatment methods and reducing damage to normal cells. This approach holds the promise of improving the treatment outcomes of cancer and other diseases.


2.3 Treatment tolerance and resistance

Treatment tolerance and resistance refer to the phenomenon where disease cells, especially in the context of cancer, gradually weaken or no longer respond as expected to treatment during the course of therapy. This may lead to disease deterioration or further spread. Treatment tolerance and resistance are common challenges in the clinical medical field, as they limit the effectiveness of treatment.


Treatment tolerance refers to the gradual weakening or loss of sensitivity to treatment in disease cells that initially responded to therapy. This may be due to mutations or changes in biological mechanisms within the cells, enabling them to resist the effects of treatment. Treatment tolerance can lead to disease recurrence or accelerated progression. Treatment resistance refers to disease cells exhibiting resistance to treatment either before receiving therapy or shortly after the initiation of treatment. This may be due to pre-existing resistance mechanisms within the cells or the rapid loss of the initial response to treatment.


The reasons for treatment tolerance and resistance are diverse. They may include intra-cellular genetic mutations, selective pressure induced by treatment, the presence of different subgroups within cancer cells, metabolic changes in treatment drugs, and so on. These factors enable cancer cells to adapt and overcome the effects of treatment.


Overcoming treatment tolerance and resistance is a crucial research area. Scientists and doctors are making efforts to develop new treatment strategies to address these issues. This may involve the use of different therapeutic drugs or combination therapy approaches, personalized treatment plans, and a deeper understanding of the biological mechanisms behind tolerance and resistance.


3 Case Study Analysis

3.1 Application of Imatinib in chronic myeloid leukemia

Imatinib is a tyrosine kinase inhibitor widely used in the treatment of chronic myeloid leukemia (CML) (Figure 3). It is a targeted therapy drug that disrupts the abnormal tyrosine kinase enzyme activity in leukemia cells, thereby inhibiting the progression of the disease.



Figure 3 Myelogram of chronic myeloid leukemia


Imatinib is a first-line treatment for chronic myeloid leukemia (CML) and is commonly used for newly diagnosed patients in the chronic phase of CML. It is the first targeted therapy successfully applied in the treatment of CML and is widely used in clinical practice. In CML patients, a specific chromosomal abnormality, known as the Philadelphia chromosome, is often present, leading to the production of the BCR-ABL fusion protein. This fusion protein has kinase activity, stimulating abnormal proliferation of leukemia cells. Imatinib works by inhibiting the activity of the BCR-ABL kinase, thereby interrupting its signaling and suppressing the growth of leukemia cells. The use of imatinib has significantly improved the survival rate and quality of life for CML patients. Most patients can maintain the chronic phase by continuously taking imatinib, and in first-line treatment, many patients can achieve sustained molecular and clinical responses. Imatinib is also used to treat early and accelerated phase CML, but treatment at these stages may require higher doses of imatinib or a switch to other targeted therapies (Song et al., 2023).


Some patients may develop resistance to imatinib during treatment, meaning their leukemia cells start to lose sensitivity to imatinib. In such cases, doctors may consider adjusting the treatment strategy, such as increasing the dose of imatinib or trying other targeted therapy drugs, such as second and third-generation tyrosine kinase inhibitors.


Imatinib, as a milestone drug in the treatment of chronic myeloid leukemia, is a highly effective therapeutic option for CML patients. However, treatment strategies need to be individually tailored based on the patient's condition and treatment response to ensure optimal therapeutic outcomes.


3.2 Success of Osimertinib in lung cancer

Osimertinib is a targeted therapy drug widely used in non-small cell lung cancer (NSCLC), especially in patients with epidermal growth factor receptor mutations. The application of Osimertinib has achieved significant success in the treatment of lung cancer (Figure 4).



Figure 4 Before and after comparison of Osimertinib in the treatment for lung cancer


The primary function of Osimertinib is to inhibit EGFR mutations, especially some common EGFR T790M mutations. These mutations are prevalent in NSCLC, particularly when patients develop resistance after receiving other EGFR inhibitors. Osimertinib inhibits the EGFR kinase activity associated with these mutations, disrupting the growth signals of cancer cells, thereby extending the patient's overall survival. The application of Osimertinib allows many NSCLC patients with EGFR mutations to effectively manage issues related to treatment resistance. Previous EGFR inhibitor treatments might lead to the emergence of resistant mutations like T790M, but Osimertinib can successfully suppress these resistant mutations, allowing patients to continue benefiting from the treatment (Zhang and Liu, 2022).


The use of Osimertinib has significantly improved the treatment response and survival rates of patients with EGFR-positive non-small cell lung cancer (NSCLC). Studies indicate that, compared to traditional EGFR inhibitors, Osimertinib can provide a longer progression-free survival (PFS) and overall survival (OS). Its successful application underscores the importance of personalized medicine. Based on the patient's EGFR mutation status, doctors can tailor the most suitable treatment plan for each patient, enhancing treatment effectiveness.


Osimertinib has lower side effects, allowing more patients to undergo long-term treatment, thereby extending survival while maintaining a higher quality of life. This provides a more effective treatment option, especially for those patients who have developed resistance. This success highlights the potential of targeted treatment strategies, emphasizing the importance of personalized and mutation-specific treatments, bringing hope to lung cancer patients.


3.3 Comparison of targeted therapy and traditional treatment

Compared to traditional treatment methods, targeted therapy has several significant advantages and distinctions in the treatment of cancer and other diseases.


Targeted therapy intervenes more precisely in disease-related biomolecules or signaling pathways, aiming at key factors of the disease more accurately compared to traditional treatment methods. This reduces damage to normal cells, alleviating the toxic side effects of treatment. The application of targeted therapy typically relies on the specific molecular characteristics of patients, such as genetic variations or biomarkers. This means treatment plans can be better tailored to meet the disease characteristics of each patient, enhancing treatment effectiveness. Targeted therapy can effectively address the issue of drug resistance. By inhibiting disease cells through different mechanisms, including resistant subgroups of cells, it reduces the risk of resistance. Targeted therapy drugs focusing on specific genetic variations have significantly improved the survival rates of patients with certain types of cancer, outperforming traditional treatment methods in some cases. Targeted therapy has various mechanisms of action suitable for different types of cancer and diseases. This provides doctors with more treatment options, helping overcome treatment tolerance and resistance. Traditional treatment methods, such as radiation therapy and chemotherapy, often induce severe side effects on healthy normal cells. Targeted therapy is generally more selective, reducing the risk of these side effects. Targeted therapy is typically provided in the form of oral medications, eliminating the need for invasive surgery or prolonged hospitalization, thus improving the convenience and quality of life for patients.


Although targeted therapy has numerous advantages, it also faces several challenges, including the development of drug resistance, high drug costs, and the possibility that certain patients may not benefit from it. Therefore, when devising treatment plans, doctors typically need to carefully consider the patient's circumstances, including the molecular characteristics of the disease and potential issues related to drug resistance, to determine the most suitable treatment approach.


4 Summary and Outlook

Targeted therapy has achieved significant success in cancer treatment. By precisely intervening in the key molecular targets or pathways of cancer cells, targeted therapy provides a more effective and precise treatment approach. For cancers driven by specific genetic mutations, these therapeutic methods can significantly improve patients' survival rates and quality of life. This underscores the importance of molecular diagnostics and personalized treatment to ensure that each patient receives the most suitable treatment for their disease characteristics. The significance of targeted therapy lies in its revolutionary change to the paradigm of cancer treatment. Traditional cancer treatment methods, such as chemotherapy and radiation therapy, while effective, often come with severe side effects, causing irreversible damage to healthy tissues. In contrast, targeted therapy can more accurately identify and intervene in the abnormal growth and differentiation mechanisms of cancer cells, reducing unnecessary side effects. This not only improves the quality of life for patients but also lowers the overall cost of treatment (Bai et al., 2022).


Targeted therapy for specific genetic mutations in cancer highlights the potential of personalized medicine. The continuous advancement of modern medical technology allows doctors to have a more comprehensive understanding of the disease characteristics of each patient, including genetic variations and biomarkers. The core idea of personalized medicine is to consider patients as unique individuals, taking into account their genetic characteristics, lifestyle, environmental factors, and the molecular mechanisms of the disease. Through precise molecular diagnostics, doctors can better understand the cancer characteristics of each patient, enabling the selection of the most suitable treatment. This not only improves the effectiveness of treatment but also reduces unnecessary treatments and associated side effects.


The successful application of targeted therapy has provided valuable insights into the field of cancer treatment. It underscores the critical nature of personalized treatment, encouraging the medical community to delve deeper into the molecular mechanisms of diseases to identify new therapeutic targets. Additionally, targeted therapy emphasizes the necessity for collaboration and innovation, urging various sectors to work together in developing more numerous and effective targeted treatment drugs. This paves the way for new directions in cancer research and treatment, offering hope and improved quality of life for a greater number of patients in the future.


In the future, targeted therapy for specific genetic mutations in cancer will continue to achieve more successes. With the continuous advancements in genetics and molecular biology, we will gain a better understanding of the molecular mechanisms of diseases, enabling the identification of more treatment targets. Simultaneously, personalized medicine will become more refined and widely applied, ensuring that each patient receives the most suitable treatment plan. Additionally, researchers will persist in addressing issues of treatment tolerance and resistance, working towards the development of more targeted treatment strategies to extend the effectiveness of treatments for patients. Collaboration and interdisciplinary research will also play a crucial role in fostering innovation and advancement in targeted therapy.



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