Cancer and Neoplasms

Cancer

• Cancer is an abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should.
• Neoplasms can be benign (not cancer) or malignant (cancer).
• Benign neoplasms may grow large but do not spread into, or invade, nearby tissues or other parts of the body.
• Malignant neoplasms can spread into, or invade, nearby tissues and also spread to other parts of the body through the blood and lymph systems.

Causes of Cancer

• Acquired mutations can occur due to exposure to environmental carcinogens.
• Inherited mutations can be hereditary and predispose to certain types of cancer.
• Spontaneous mutations can occur at a frequency of approximately 10^(-7) to 10^(-6) per cell per generation.
• Oxidative stress can also contribute to cancer.

Carcinogenesis

• Direct carcinogens can interact with DNA without prior enzyme activation.
• Indirect carcinogens require enzyme activation to become the ultimate carcinogen and then interact with DNA.
• Initiation is the stage where exposure to a chemical causes irreversible DNA damage.
• Promotion comprises the stage at which an initiated cell begins to grow and proliferate abnormally.
• The cumulative effect of these stages is a neoplasm.

Viral Oncogenesis

• Integration of viral DNA with the host DNA can result in various events such as deregulation of the cell cycle, inhibition of apoptosis, and abnormalities of cell signaling pathways.

Oncogenes and Tumor Suppressor Genes

• Oncogenes encode proteins that can drive the growth of cancer cells and are derived from proto-oncogenes.
• Tumor suppressor genes encode proteins that normally suppress cell growth, but which are inactivated when altered by mutations.

Chromosomal Abnormalities

• Gene amplification can result in homogeneous staining regions on chromosomes or as double minute chromosomes.
• Chromosomal translocations can result in the activation of oncogenes, such as the MYC gene.

Cytokines

• Many different interleukins have been isolated, along with interferons and other proteins/polypeptides, which are referred to as cytokines.

Cancer Prevention

• Reduce tobacco use
• Increase physical activity
• Control weight
• Improve diet
• Limit alcohol consumption
• Use safer sex practices
• Routine cancer screening tests
• Avoid excess exposure to the sun

Cell Cycle Regulation

• The retinoblastoma protein (Rb) regulates the cell cycle and can be phosphorylated to release E2F, allowing the expression of genes necessary for S-phase progression.
• p53 is activated by a range of cellular stress signals and can regulate the cell cycle.

Cell Adhesion Molecules (CAMs)

• Cadherins, immunoglobulin (Ig) superfamily, integrins, and selectins are examples of CAMs.
• CAMs can be homophilic or heterophilic and play a crucial role in cell-cell adhesion and migration.

Metastasis

• An epithelial-to-mesenchymal cell transition is often found in cancers, allowing increased movement of potentially metastatic cells.
• Metastasis is relatively inefficient, and metastatic cells must evade the immune system to survive.
• Changes in cell surface molecules, such as CAMs, and increased proteinase activity facilitate invasion.
• Metastasis gene signatures can be detected by transcriptome/exome analysis and can be of prognostic value.

Metabolic Changes in Cancer

• Changes in metabolism have been observed in most cancer cells.
• Metabolic protein-encoding genes are commonly mutated in various types of cancer.

Tumor Biomarkers

• Alpha-fetoprotein (AFP), calcitonin (CT), carcinoembryonic antigen (CEA), human chorionic gonadotropin (hCG), monoclonal immunoglobulin, and prostate-specific antigen (PSA) are examples of tumor biomarkers.
• These biomarkers can be elevated in the blood of patients with non-cancerous diseases, so interpretation of elevated results must be made with caution.
• Their main uses are to follow the effectiveness of treatments and to detect recurrences.