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Biochemical Mechanism of Tumorigenesis

Tumorigenesis, also known as oncogenesis or carcinogenesis, is the complex process through which normal cells transform into cancerous tumors. This transformation unfolds over time and involves a variety of genetic and environmental factors that disrupt the normal balance of cell growth and death. Understanding what happens at the biochemical level can shed light on this intricate process.

What Are Tumors?

Before exploring the biochemical mechanisms, it’s important to understand what tumors are. The term “tumor” comes from the Latin word tumere, meaning “to swell.” Tumors, also called neoplasms, are masses of abnormal cells that divide uncontrollably due to DNA mutations. There are two main types of tumors:

  • Benign Tumors: These are non-cancerous, grow slowly, and do not spread to other parts of the body. However, they can cause problems by compressing nearby organs, such as a large lung tumor that might impede breathing.
  • Malignant Tumors: These are cancerous, grow more rapidly, invade nearby tissues, and can spread to distant parts of the body through a process known as metastasis. Common metastatic sites include the liver, lungs, brain, and bones.

Types of Tumors (JAMA oncology, 2020)


Causes of Tumor Formation

The human body continuously produces new cells to replace old or damaged ones. This process is usually tightly regulated. However, when cells fail to die off or start dividing too quickly, tumors can form. Several factors can disrupt this balance:

  1. Gene Mutations: Changes in genes, such as BRCA genes linked to breast cancer, can lead to uncontrolled cell multiplication.
  2. Inherited Conditions: Syndromes like Lynch syndrome or neurofibromatosis (NFS) can increase cancer risk.
  3. Family History: Having a close family member with cancer may raise your risk.
  4. Smoking: Exposure to tobacco smoke, whether direct or second-hand, is a known carcinogen.
  5. Toxins: Substances like benzene or asbestos can trigger tumor growth.
  6. Radiation Exposure: Previous exposure to radiation is a known risk factor for cancer.
  7. Viruses: Certain viruses, such as HPV (Human Papillomavirus) and HBV (Hepatitis B Virus), can cause specific types of cancer.

Phases of Tumorigenesis

Tumorigenesis is a multistage process that consists of three main phases:

  1. Initiation: This initial phase involves genetic mutations in normal cells. These mutations may be spontaneous or caused by carcinogens—substances or agents that can lead to cancer. These genetic changes set the stage for tumor development.
  2. Promotion: Following initiation, the affected cells are stimulated to proliferate. This phase involves prolonged exposure to promoting stimuli, allowing the mutated cells to form a pre-malignant tumor.
  3. Progression: In this final stage, the pre-malignant tumor becomes fully cancerous. The cells continue to mutate and divide uncontrollably, gaining the ability to invade nearby tissues and metastasize to other parts of the body. At this point, the tumor is malignant and poses a significant health threat.

Mechanism of Carcinogenesis (Sharma et al., 2023)


The Role of DNA Damage

A central factor in tumorigenesis is DNA damage. Every day, our DNA is exposed to both internal (endogenous) and external (exogenous) sources of damage:

  • Endogenous Sources: Normal cellular processes can create reactive oxygen species.
  • Exogenous Sources: UV light, radiation, and harmful chemicals are external factors that can damage DNA.

DNA damage can lead to mutations in critical genes, such as tumor suppressor genes or oncogenes. Over time, these mutations accumulate, pushing cells toward malignancy.

DNA damage plays a central role in many biological processes linked to cancer (malignant tumor) (Basu, 2018)


Conclusion

The biochemical mechanism of tumorigenesis is a complex, multistage process driven by genetic mutations and environmental factors. From the initial DNA damage to the uncontrolled growth and spread of malignant cells, understanding these mechanisms is crucial for developing effective treatments and preventive strategies for cancer. By targeting these pathways early, therapies such as surgery, chemotherapy, and radiotherapy can effectively manage or even cure cancer if detected in a timely manner.


References

Basu, A. K. (2018). DNA Damage, Mutagenesis, and Cancer. International Journal of Molecular Sciences, 19.

Patel, A. (2020). Tumor Classification and Treatment. JAMA Oncology, 6(9), 1488. doi:10.1001/jamaoncol.2020.2592. Link

Whelan, S. (2022). Benign vs. Malignant Tumors. Link

Cancer Research UK. (2023). How Cancers Grow. Link

National Cancer Institute. (2021). What Is Cancer. Link

Costa, J. (2024). Cancer. Encyclopedia Britannica. Link

Bi, Q., Wu, J.-Y., Qiu, X.-M., Zhang, J.-D., Sun, Z.-J., Wang, W. (2022). Tumor-Associated Inflammation: The Tumor-Promoting Immunity in the Early Stages of Tumorigenesis. Journal of Immunology Research, 2022, 1–13. doi:10.1155/2022/3128933

Rycaj, K., & Tang, D. G. (2015). Cell-of-Origin of Cancer vs. Cancer Stem Cells: Assays and Interpretations. Cancer Research, 75(19), 4003–4011.

Devi, P. U. (2018). Basis of Carcinogenesis. Health Administration, 17, 16–24.

Loeb, L. A., & Harris, C. C. (2008). Advances in Chemical Carcinogenesis: A Historical Review and Prospective. Cancer Research, 68, 6863–6870.

Moga, M., Bălan, A., Anastasiu, C.-V., Oana, D., Neculoiu, C.-D., & Gavris, C. (2018). An Overview on the Anticancer Activity of Azadirachta indica (Neem) in Gynecological Cancers. International Journal of Molecular Sciences, 19, 3898. doi:10.3390/ijms19123898

Kotecha, R., Takami, A., & Espinoza, J. L. (2016). Dietary Phytochemicals and Cancer Chemoprevention: A Review of the Clinical Evidence. Oncotarget.

American Society of Clinical Oncology (ASCO). (2022). Understanding Cancer Risk. Link

Sharma, A., Sharma, L., Nandy, S., Payal, N., Yadav, S., Cruz, C., Anwer, M. K., Khan, H., Behl, T., & Bungau, S. (2023). Molecular Aspects and Therapeutic Implications of Herbal Compounds Targeting Different Types of Cancer. Molecules, 28, 750.

Written By:      Emmanuel Ogunmokun  Research Scientist

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