Introduction:
Cancer is a long-term disorder, a phase that encompasses hundreds of diseases that affect virtually every region of the body, many of which are potentially fatal. Cancer occurs when abnormal cells divide uncontrollably, resulting in a tumor that can spread or a colony of abnormal cells in the circulation. Cancer develops when deoxyribonucleic acid (DNA) mutations or inherited defective genes cause one or a few cells to grow and reproduce excessively. However, the immune system fails to recognize and eliminate these cells effectively. This might be related to abnormalities in tumor suppressor genes, which regulate cell growth and death.
What Are the Types of Cancer?
The most common types of cancer are as follows:
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Carcinoma: Starts in one organ and spreads to others, such as the intestines, ovaries, lungs, breasts, or pancreas.
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Sarcoma: Tumors of bone, muscle, fat, blood vessels, cartilage, or other soft or connective tissues.
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Melanoma: It is skin cancer of melanin-forming cells.
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Lymphoma: Tumors that affect the white blood cells known as lymphocytes.
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Leukemia: It results in immature or aberrant cells that inhibit the creation of normal blood cells.
Is Inflammation a Risk Factor for Cancer?
Most gene mutations are not inherited and are caused by various conditions such as age, carcinogenic chemicals, smoking, sun exposure, obesity, and a lack of exercise. Furthermore, persistent inflammation is a well-known risk factor. Some kinds of cancer have inflammatory symptoms before they become malignant. On the other hand, changes generated by an oncogene create an inflammatory environment in other forms of cancer. In both circumstances, inflammation in the tumor microenvironment promotes tumor growth.
Which Inflammatory Cells Contribute to Cancer?
The following signaling molecules of inflammation cause cancer:
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Cytokines: Promote cell proliferation and the recruitment of immune cells and maintain the tumor microenvironment.
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Inducible Nitric Oxide Synthase: Activates transcription factors in precancerous and cancerous tumors. It also triggers oxidative DNA damage.
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The Transcription Factor Nf-Kappa Beta: Promotes tissue invasion, metastasis, and apoptosis protection for altered cell addition. In addition, it increases the production of proinflammatory mediators.
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Cox2: It is overexpressed in various malignancies linked with inflammation as it catalyzes the synthesis of lipid-based inflammatory mediators. It also aids in the maintenance of a chronic inflammatory condition.
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PGE2: Promotes angiogenesis (formation of new blood vessels) during inflammation. As a result, proinflammatory mechanisms in the tumor microenvironment are activated.
What Is the Mechanism of Action of Inflammation-Associated Cancers?
The tumor microenvironment comprises various resident cell types, including adipocytes, fibroblasts, and migratory hematopoietic cells such as macrophages, neutrophils, and mast cells. In addition, adaptive and innate immune system members are located in the microenvironment. Macrophages enhance the persistent inflammatory state of the tumor microenvironment. Collaborating with recruited neutrophils, macrophages, mast cells, and eosinophils raises the concentration of reactive oxygen and nitrogen species in the tumor microenvironment to enhance the body's natural defense against infection. However, higher reactive oxygen and nitrogen species concentrations can cause mutagenesis via DNA damage or altered gene expression in growing cells. Furthermore, the tumor inflammatory microenvironment promotes basement membrane breakage, thus leading to tumor cell invasion and migration.
What Are the Signs of Cancer-Associated Inflammation?
The signs of cancer-associated inflammation are as follows:
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Invading leukocytes.
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Increased production of cytokines such as tumor necrosis factor-alpha (TNF-alpha).
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Increased interleukins.
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Signals governing the development of new blood vessels.
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Tissue rebuilding.
What Is the Role of Inflammation in Cancer?
Inflammation, the body's natural defensive system, plays a significant role in establishing the tumor microenvironment and, ultimately, the advancement of cancer. Surprisingly, altered cells can use this natural defensive system to aid their growth and survival. Oncogene activation, which is required for cancer formation, is associated with increased production of immune-influencing molecules such as cytokines and cells that are either directly tumor-promoting or immunosuppressive. This is because tumors develop and are invaded by many immune cells. Inflammation favors the following roles of cancer:
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Carcinogenesis (cancer formation).
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Malignant transformation.
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Tumor growth.
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Tumor invasion.
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Metastatic spread.
Mutations in RAS genes, primarily KRAS, play a crucial role in up to 30 % of all human cancers, suggesting that the K-Ras protein has a causal function in carcinogenesis. K-Ras generates the pro-inflammatory cytokines interleukin 6 and interleukin 8, which block normal cell death and accelerate the formation of new blood vessels to supply oxygen and nutrients to the tumor.
What Is Immunosurveillance?
Following the production of pro-inflammatory cytokines, chronic inflammation is caused by the persistence of inflammation-initiating substances or a failure of the systems required to eliminate inflammation. This process of inflammation initiation and elimination is known as immunosurveillance.
What Is Cancer Therapy-Induced Inflammation?
Therapy-induced inflammation arises in response to different anti-cancer therapies, including chemotherapy, radiation, and immune infiltration produced by various biologic therapies or immunotherapies. Current immunotherapies rely on immune system activation in the tumor following treatment. This procedure can aid in developing anti-tumor immune responses, which will work with traditional therapy. In some situations, releasing ATP and HMGB1 from dying tumor cells might trigger the production of IL-1 and other immunostimulatory cytokines. This, together with enhanced tumor production, may activate and maintain de novo anti-tumor T cell responses or may result in immunosuppression.
How Can Inflammation-Associated Cancers Be Prevented?
Anti-inflammatory chemicals, synthetic and natural, are commonly used in cancer therapy. The selective Cox2 inhibitor revealed markedly decreased chemopreventive effects in colon and gastrointestinal tumor research. Antioxidants such as epicatechin from tea, resveratrol from grapes and red wine, the plant ingredient curcumin, and sulforaphane from broccoli have also been shown to be beneficial against tumors. Studies with cultured cells and antiviral models have shown that inflammation is active in tumor formation and that anti-inflammatory drugs help inhibit and delay tumor growth and progression. Curcumin, a natural substance, works by inhibiting signals.
Conclusion
The functional link between inflammation and cancer is still not very clear. Although it is evident that cell proliferation alone does not cause cancer, persistent cell proliferation in an environment rich in inflammatory cells, growth factors, and DNA-damage-promoting cells potentiates cancer growth risk. For example, tumor development in gastrointestinal stromal tumors (GIST) is preceded by inflammation of gastrointestinal tissues. While it is well acknowledged that chronic inflammation plays a vital role in establishing the tumor microenvironment, further research is needed to identify the particular molecular mechanisms contributing to its initiation and progression. Thus, it is essential to investigate the molecular processes of inflammation in cancer to lead to the discovery of novel targets for improved diagnosis and treatment.
