Cancers

Cancers are a group of diseases characterized by uncontrolled cell division, which leads to the formation of a mass of abnormal cells known as a tumour. If a tumour invades surrounding tissue, it is defined as cancer.

Control of Cell Division and Tumour Formation

Normally, the cell cycle and mitosis are precisely controlled by genes. Cells typically stop dividing once enough new cells are produced. However, if a mutation occurs in a gene that controls cell division, cells can grow out of control. This uncontrolled division results in a tumour.

Tumours can be categorized into two types:

• Malignant tumours are cancerous. They typically grow rapidly, invade, and destroy surrounding tissues. Cells from malignant tumours can break off and spread to other parts of the body through the bloodstream or lymphatic system, a process called metastasis, which is considered the most dangerous characteristic of cancer.

• Benign tumours are non-cancerous. They usually grow slower than malignant tumours and are often covered in fibrous tissue, which prevents them from invading other tissues. While often harmless, some benign tumours can become malignant.

Causes and Risk Factors for Cancer

Cancer development is linked to mutations in specific genes and is influenced by both genetic and environmental factors.

Key genetic factors include:

• Proto-oncogenes: Normally, these genes stimulate cell division by producing proteins that make cells divide. If a mutation causes a proto-oncogene to become overactive, it is called an oncogene, leading to uncontrolled cell division and tumour formation.

• Tumour suppressor genes: These genes normally slow cell division by producing proteins that stop cells from dividing or cause them to self-destruct (apoptosis). If a mutation inactivates a tumour suppressor gene, the protein it codes for is not produced, leading to uncontrolled cell division and tumour development. Examples include mutations in the RB1 gene (linked to retinoblastoma) and BRCA1 and BRCA2 genes (linked to breast and ovarian cancers).

• Abnormal methylation: This epigenetic modification can affect gene expression. Hypomethylation of proto-oncogenes can cause them to act as oncogenes, increasing cell division. Hypermethylation of tumour suppressor genes can switch them off, preventing the production of proteins that slow cell division, leading to uncontrolled mitosis and tumour growth.

Environmental factors (carcinogens) that increase cancer risk include:

• Radiation: Ionizing radiation (X-rays, gamma rays, alpha/beta particles) and non-ionizing radiation (UV light) can damage DNA, causing mutations.

• Chemicals: Substances like tar in tobacco smoke and asbestos are carcinogens that can cause mutations in DNA. Benzopyrene in tobacco smoke, for example, can interfere with DNA replication and react with the p53 gene, which is often inactivated in lung cancers.

• Hormones: Increased exposure to oestrogen, often due to factors like early menstruation, late menopause, or hormone replacement therapy (HRT), is thought to increase the risk of some breast cancers by stimulating cell division and potentially introducing mutations directly into DNA.

• Lifestyle choices: Smoking, increased alcohol consumption, and a high-fat diet have all been linked to an increased chance of developing some cancers. It's important to note that correlation does not always mean causation, and multiple factors can be at play.

Tumour cells differ from normal cells in several ways: they often have a larger and darker nucleus (sometimes more than one), an irregular shape, do not produce all correct proteins, have different surface antigens, and do not respond to growth-regulating processes, dividing more frequently.

Cancer and Telomeres

In many specialized cells, telomeres (protective DNA sequences at the ends of chromosomes) shorten with each cell division. This shortening is considered a mechanism of aging, as very short telomeres can lead to cell death. However, cancer cells are often "immortal" because they typically renew their telomeres after each division using the enzyme telomerase. Research is exploring inactivating telomerase in cancer cells as a way to prevent their unlimited division and subsequent tumour growth.

Cancer Treatment

Cancer treatments are designed to control the rate of cell division in tumour cells by disrupting the cell cycle, which aims to kill tumour cells.

• Chemotherapy drugs can prevent the synthesis of enzymes needed for DNA replication (e.g., methotrexate) or prevent spindle fibre formation (e.g., vincristine), disrupting the cell cycle and forcing cell death. These treatments can also kill normal dividing cells, leading to side effects like hair loss.

• Radiation therapy (radiotherapy) damages tumour cell DNA, causing them to die and the tumour to shrink.

• Targeted therapies, such as monoclonal antibodies (Mabs), offer a more specific approach. Mabs can be designed to:

  • Bind to tumour markers (antigens unique to cancer cells) on the cell surface, making cancer cells visible to the immune system for destruction.

  • Block growth signals on the surface of cancer cells to prevent their uncontrolled growth.

  • Stop the formation of new blood vessels that supply malignant tumours.

  • Deliver radiation specifically to cancer cells, minimizing damage to normal tissue.

  • An example is Herceptin® (Trastuzumab), which binds to the HER2 receptor on breast cancer cells to suppress division.

• Gene therapy holds potential for future treatments, aiming to replace faulty alleles in cancer cells with working versions.

• Preventative measures and early diagnosis involve screening for known cancer-causing mutations (e.g., RAS mutations in bowel cancer or APC gene mutations in colon cancer).

Ongoing research continues to enhance understanding and treatment strategies for cancer.