Introduction: Cancer, as one of the major health challenges of today, due to the biological complexities and variety of tumors, its effective treatment has become a global problem. Conventional treatment methods include surgery, chemotherapy, radiotherapy, and targeted therapies, each of which has its own advantages and disadvantages and may be associated with significant side effects. In particular, surgery and chemotherapy face certain limitations and often require careful management of side effects. In this regard, anti-cancer vaccines have been considered as a new therapeutic approach. These vaccines are divided into two main categories: preventive vaccines, which are designed to prevent cancer in high-risk individuals, and therapeutic vaccines, which are used to stimulate the body's immune response to fight cancer cells in cancer patients. This article examines recent advances in the field of anti-cancer vaccines, including benefits, challenges and problems in this field, and analyzes the performance of various vaccines and strategies to improve their effectiveness. The aim of this review is to provide an overview of the current status and future prospects in the use of anticancer vaccines as a complementary and novel therapy.
Methods: Introduction: Cancer is one of the most complex and life-threatening human diseases, resulting from genetic and epigenetic changes in cells. These changes disrupt normal cellular processes such as cell division, differentiation, and apoptosis. Cancer occurs when the body's cells begin to proliferate uncontrollably, forming malignant tumors. In this process, cancer cells escape the natural mechanisms of cellular control and circumvent the body's defense systems to promote their own growth.
1. Mechanisms of Cancer Formation Cancer is a multi-stage disease arising from numerous alterations in the genome of cells. These changes may be caused by environmental factors (such as carcinogenic chemicals, radiation, and viruses) or internal factors (such as inherited genetic mutations). The genes involved in cancer are generally classified into three categories:
1.1. Oncogenes: Oncogenes are mutated versions of normal genes called proto-oncogenes, which are naturally involved in biological processes like growth and cell division. Mutations or overexpression of these genes can lead to their abnormal activation and tumor development [1].
1.1.1. Mechanisms of Oncogene Action Oncogenes contribute to cancer through several mechanisms:
Point mutations: These mutations may lead to changes in the amino acid sequence of proteins, resulting in abnormal activity. For instance, a mutation in the RAS gene can lead to the continuous production of active RAS proteins, sending constant growth signals [2].
Overexpression: Increased expression of an oncogene can lead to the overproduction of proteins responsible for cell division and growth. Genes such as MYC and HER2 exemplify this mechanism [3].
Gene fusion: In some cases, fusion of oncogenes with other genes can result in abnormal proteins. For example, gene fusions in leukemia (e.g., BCR-ABL) produce fusion proteins with abnormal activity [4].
1.2. Role of Oncogenes in Cancer Oncogenes play various roles in different cancers:
Breast cancer: The HER2/neu oncogene is one of the most important in breast cancer, promoting increased growth and proliferation of cancer cells. Targeted therapies like trastuzumab (Herceptin) have been designed to inhibit the activity of this protein [5].
Lung cancer: Genes such as RAS and EGFR play critical roles in non-small cell lung cancer (NSCLC). Alterations in these genes can lead to disease progression and resistance to standard therapies [6].
Leukemia: In blood cancers such as acute myeloid leukemia (AML), mutations in the FLT3 gene contribute to the development and progression of the disease [7].
2. Tumor Suppressor Genes: Tumor suppressor genes are key regulators that control cell growth and division, preventing cancer development. These genes generally function in two ways: first, by producing proteins that help control the cell cycle and prevent abnormal cell division; second, by repairing DNA damage to avoid the genetic changes that may lead to cancer [8].
2.1. Key Tumor Suppressor Genes
p53 Gene: The p53 gene is one of the most crucial tumor suppressor genes, often referred to as the "guardian of the genome" [9]. The p53 protein helps regulate the cell cycle and induce apoptosis (programmed cell death). When DNA damage occurs, p53 halts cell proliferation, facilitating DNA repair, and if unsuccessful, it induces apoptosis [10].
BRCA1 and BRCA2 Genes: These genes are also recognized as important tumor suppressors that help repair DNA damage. Mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancers. These genes encode proteins involved in DNA repair processes [12].
PTEN Gene: PTEN is another tumor suppressor gene that regulates cellular signaling pathways, especially the PI3K/Akt pathway [13]. PTEN mutations are linked to various cancers, including prostate, breast, and thyroid cancers [15].
3. DNA Repair Genes: DNA repair genes play a crucial role in maintaining genetic integrity and preventing harmful mutations. These genes are responsible for identifying and repairing DNA damage caused by environmental, internal, or natural replication errors [20]. Dysfunction in these genes can lead to various diseases, including cancer [21].
4. The Role of the Immune System in Cancer Defense One of the body's first lines of defense against cancerous cells is the immune system, which consists of components like lymphocytes, macrophages, and natural killer (NK) cells that play a role in recognizing and destroying abnormal cells. Specifically, T cells are crucial in identifying cancer cells by recognizing cancer antigens on their surfaces and initiating the destruction process [30].
Cancer Immune Evasion Mechanisms Cancer cells can employ various mechanisms to evade immune detection:
Reduced antigen presentation: Cancer cells may reduce the expression of antigens recognized by the immune system. In particular, the downregulation of MHC class I molecules on the surface of cancer cells may result in decreased recognition by T cells [31].
Suppression of immune responses: Cancer cells can secrete chemicals like tumor growth factors and cytokines that suppress immune activity. These substances may induce regulatory T cells (Tregs), which naturally inhibit immune responses and reduce the body's ability to fight cancer [32].
Expression of inhibitory proteins: Cancer cells often express proteins such as PD-L1, which bind to inhibitory receptors like PD-1 on T cells, preventing their activation. This is one of the primary mechanisms through which cancer evades the immune system [33].
Cancer Vaccines One significant advancement in the fight against cancer is the development of cancer vaccines, aimed at boosting the immune system to recognize and destroy cancer cells. Unlike traditional vaccines that protect against viral or bacterial infections, cancer vaccines are categorized into preventive and therapeutic vaccines. These vaccines are designed to stimulate the immune system to recognize specific cancer cell antigens and activate immune cells for targeted action.
Types of Cancer Vaccines Cancer vaccines are broadly classified into several categories, each employing different mechanisms to stimulate an immune response against cancer cells:
Neoantigen-based vaccines
Dendritic cell vaccines
DNA and RNA vaccines
Peptide vaccines
Oncolytic virus vaccines
Protein-based vaccines
Tumor cell vaccines
Liposome-based vaccines
Chimeric antigen receptor (CAR) vaccines
Nanoparticle-based vaccines
Hybrid vaccines
Epitope-based vaccines
Microbiome-based vaccines
The article will further explore some of these vaccine types.
Results: Introduction: Cancer is one of the most complex and life-threatening human diseases, resulting from genetic and epigenetic changes in cells. These changes disrupt normal cellular processes such as cell division, differentiation, and apoptosis. Cancer occurs when the body's cells begin to proliferate uncontrollably, forming malignant tumors. In this process, cancer cells escape the natural mechanisms of cellular control and circumvent the body's defense systems to promote their own growth.
1. Mechanisms of Cancer Formation Cancer is a multi-stage disease arising from numerous alterations in the genome of cells. These changes may be caused by environmental factors (such as carcinogenic chemicals, radiation, and viruses) or internal factors (such as inherited genetic mutations). The genes involved in cancer are generally classified into three categories:
1.1. Oncogenes: Oncogenes are mutated versions of normal genes called proto-oncogenes, which are naturally involved in biological processes like growth and cell division. Mutations or overexpression of these genes can lead to their abnormal activation and tumor development [1].
1.1.1. Mechanisms of Oncogene Action Oncogenes contribute to cancer through several mechanisms:
Point mutations: These mutations may lead to changes in the amino acid sequence of proteins, resulting in abnormal activity. For instance, a mutation in the RAS gene can lead to the continuous production of active RAS proteins, sending constant growth signals [2].
Overexpression: Increased expression of an oncogene can lead to the overproduction of proteins responsible for cell division and growth. Genes such as MYC and HER2 exemplify this mechanism [3].
Gene fusion: In some cases, fusion of oncogenes with other genes can result in abnormal proteins. For example, gene fusions in leukemia (e.g., BCR-ABL) produce fusion proteins with abnormal activity [4].
1.2. Role of Oncogenes in Cancer Oncogenes play various roles in different cancers:
Breast cancer: The HER2/neu oncogene is one of the most important in breast cancer, promoting increased growth and proliferation of cancer cells. Targeted therapies like trastuzumab (Herceptin) have been designed to inhibit the activity of this protein [5].
Lung cancer: Genes such as RAS and EGFR play critical roles in non-small cell lung cancer (NSCLC). Alterations in these genes can lead to disease progression and resistance to standard therapies [6].
Leukemia: In blood cancers such as acute myeloid leukemia (AML), mutations in the FLT3 gene contribute to the development and progression of the disease [7].
2. Tumor Suppressor Genes: Tumor suppressor genes are key regulators that control cell growth and division, preventing cancer development. These genes generally function in two ways: first, by producing proteins that help control the cell cycle and prevent abnormal cell division; second, by repairing DNA damage to avoid the genetic changes that may lead to cancer [8].
2.1. Key Tumor Suppressor Genes
p53 Gene: The p53 gene is one of the most crucial tumor suppressor genes, often referred to as the "guardian of the genome" [9]. The p53 protein helps regulate the cell cycle and induce apoptosis (programmed cell death). When DNA damage occurs, p53 halts cell proliferation, facilitating DNA repair, and if unsuccessful, it induces apoptosis [10].
BRCA1 and BRCA2 Genes: These genes are also recognized as important tumor suppressors that help repair DNA damage. Mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancers. These genes encode proteins involved in DNA repair processes [12].
PTEN Gene: PTEN is another tumor suppressor gene that regulates cellular signaling pathways, especially the PI3K/Akt pathway [13]. PTEN mutations are linked to various cancers, including prostate, breast, and thyroid cancers [15].
3. DNA Repair Genes: DNA repair genes play a crucial role in maintaining genetic integrity and preventing harmful mutations. These genes are responsible for identifying and repairing DNA damage caused by environmental, internal, or natural replication errors [20]. Dysfunction in these genes can lead to various diseases, including cancer [21].
4. The Role of the Immune System in Cancer Defense One of the body's first lines of defense against cancerous cells is the immune system, which consists of components like lymphocytes, macrophages, and natural killer (NK) cells that play a role in recognizing and destroying abnormal cells. Specifically, T cells are crucial in identifying cancer cells by recognizing cancer antigens on their surfaces and initiating the destruction process [30].
Cancer Immune Evasion Mechanisms Cancer cells can employ various mechanisms to evade immune detection:
Reduced antigen presentation: Cancer cells may reduce the expression of antigens recognized by the immune system. In particular, the downregulation of MHC class I molecules on the surface of cancer cells may result in decreased recognition by T cells [31].
Suppression of immune responses: Cancer cells can secrete chemicals like tumor growth factors and cytokines that suppress immune activity. These substances may induce regulatory T cells (Tregs), which naturally inhibit immune responses and reduce the body's ability to fight cancer [32].
Expression of inhibitory proteins: Cancer cells often express proteins such as PD-L1, which bind to inhibitory receptors like PD-1 on T cells, preventing their activation. This is one of the primary mechanisms through which cancer evades the immune system [33].
Cancer Vaccines One significant advancement in the fight against cancer is the development of cancer vaccines, aimed at boosting the immune system to recognize and destroy cancer cells. Unlike traditional vaccines that protect against viral or bacterial infections, cancer vaccines are categorized into preventive and therapeutic vaccines. These vaccines are designed to stimulate the immune system to recognize specific cancer cell antigens and activate immune cells for targeted action.
Types of Cancer Vaccines Cancer vaccines are broadly classified into several categories, each employing different mechanisms to stimulate an immune response against cancer cells:
Neoantigen-based vaccines
Dendritic cell vaccines
DNA and RNA vaccines
Peptide vaccines
Oncolytic virus vaccines
Protein-based vaccines
Tumor cell vaccines
Liposome-based vaccines
Chimeric antigen receptor (CAR) vaccines
Nanoparticle-based vaccines
Hybrid vaccines
Epitope-based vaccines
Microbiome-based vaccines
The article will further explore some of these vaccine types.
Conclusion: conclusion
At the end of this article, it can be concluded that anti-cancer vaccines have shown high potential as a new treatment strategy in dealing with different types of cancers. Considering the challenges in traditional treatments such as chemotherapy and radiotherapy that may face severe side effects and drug resistance, anti-cancer vaccines can play an effective role as a complementary or alternative method in the management of cancer diseases.
Among the most important advantages of anti-cancer vaccines is their ability to be personalized based on the genetic characteristics of each patient. These vaccines can be designed based on specific neoantigens that are produced in cancer cells and directly stimulate the body's immune system to recognize and destroy cancer cells. This feature increases the efficiency of treatment and reduces side effects. In this context, neoantigen vaccines are one of the most promising strategies in personalized immunotherapy due to their ability to stimulate strong immune responses.
Another effective strategy in anti-cancer vaccines is the use of dendritic cells. Dendritic cells play a key role in the activation of T cells due to their high ability to absorb and process antigens. These vaccines can help fight cancer cells by strengthening the body's immune system. Although the production of these vaccines is complex and expensive, they have shown promising results in the treatment of various cancers, including melanoma and prostate cancer.
However, there are many challenges in the development and application of these vaccines. One of these challenges is the cost and time-consuming process of producing vaccines due to the need for genomic sequencing and bioinformatics analysis. Also, the immune response to these vaccines may vary among different patients, which requires further research to optimize processes and increase the effectiveness of treatments.
In general, anti-cancer vaccines as a new and complementary strategy in the treatment of cancers have shown great potential and have a bright future in the field of cancer treatment. Nevertheless, there is still a need for more research and improvement of the production and application processes of these vaccines in order to achieve a significant improvement in the control and treatment of cancer.
Keywords: conclusion
At the end of this article, it can be concluded that anti-cancer vaccines have shown hig