PATH 2300 Week 4

Cancer: A Disease of Cell Growth, Division, and Differentiation

• Cancer is a class of diseases characterized by altered differentiation, uncontrolled cell division, and genetic mutations.
• Prostate cancer is most common in males, and breast cancer is most common in females.

Neoplasia

• A tumor is an abnormal growth of tissue, not necessarily cancerous.
• Neoplasia is abnormal, disorganized growth forming a neoplasm (benign or malignant).
• Cancer is malignant growth, not benign.
• In situ means the growth is in the same place.

Classifying Neoplasms

Benign Neoplasms

• Benign cells may perform normal functions.
• They are not life-threatening.
• Local effects can range from minor to lethal, including occupying space, obstructing blood flow or air flow, obstructing passages, compressing healthy tissue, ulcerating, becoming infected, or hemorrhaging.

Malignant Neoplasms

• Malignant cells are anaplastic (undifferentiated).
• They are more aggressive and invasive compared to benign neoplasms.
• A characteristic clinical course progresses rapidly to metastasis and death.
• Angiogenesis is the formation of new blood vessels crucial for tumor growth.

Staging of Cancers

• Cancer stage indicates the extent of spread.
• Staging is a significant predictor of survival.
• Treatment often depends on the cancer stage.
• Two common methods are the TNM system (tumor, nodes, metastases) and the stages 0-IV system.

Cancer Names (Tumour Nomenclature)

• The prefix for a tumor's name depends on the tissue of origin (e.g., leiomyo- for smooth muscle).
• Benign tumors are named with the prefix + oma (e.g., leiomyoma).
• Malignant tumors are named with the prefix + carcinoma (for epithelial tissue) or sarcoma (for mesenchymal tissue).
• Adenoma is a benign glandular tumor.
• Squamous cell carcinoma is a malignant squamous epithelial tumor.
• Fibrosarcoma is a malignant fibrous connective tissue tumor.
• Chondroma is a benign cartilaginous tumor.
• Leiomyosarcoma is a malignant smooth muscle tumor.
• Melanoma is a malignant melanocyte tumor.

Characteristics of Cancer Cells

• Cancer cells exhibit several abnormalities:
  • Loss of differentiation (anaplasia).
  • Genetic instability.
  • Growth factor independence.
  • Autonomous behavior (loss of connections with neighbors).
  • Limitless replicative potential (cells don't age).
  • Avoidance of apoptosis (programmed cell death).
  • Promotion of angiogenesis.
  • Tissue invasion and metastasis.

Genetics and Environmental Basis of Cancer

• Cancer development is a multistage process involving genetic damage.
• Most cancers arise spontaneously, but frequency of mutation increases with exposure to carcinogens (e.g., cigarette smoke).
• The cell cycle is crucial to cancer development.

Cell Cycle Control

• Proto-oncogene activation leads to inappropriate cell growth and division (dominant mutation).
• Tumor suppressor gene inactivation prevents the normal arrest of cell cycle progression (recessive mutation).
• Proto-oncogenes are normal genes that activate cell growth and division (example: VEGF, EGFR, transcription factors).
• Oncogenes are mutated proto-oncogenes that always remain "on," driving tumor formation.
• A gain of function in proto-oncogenes causes tumor formation.

Tumor Suppressor Genes

• Tumor suppressor genes produce proteins that inhibit growth, enhance differentiation, promote DNA repair, and induce apoptosis.
• Loss of function in tumor suppressor genes causes tumor formation.
  • Example genes: p53, Rb, BRCA1

Ras Protein

• Located on the plasma membrane, Ras conveys growth factor signals to the nucleus.
• Mutations make Ras an oncogene, always signaling cell division.
• Present in about 30% of human cancers.

p53 (Tumor Suppressor Gene)

• A key tumor suppressor gene.
• Produces p53 protein that activates DNA repair, growth inhibition, and apoptosis.

Tumor Heterogeneity

• Tumors vary in their genetic makeup and behavior (heterogeneity).

Gene-Environment Interaction

• Environmental factors influence cancer development.
• Lifestyle and environmental factors explain varied cancer rates internationally.

Metastasis

• Metastasis is the spread of cancer cells from a primary tumor to a distant site.
• Cancer cells detach from the primary tumor, travel to a distant site, and form a secondary mass..
• Pathways include seeding, lymphatic spread, and hematogenous spread.

Metastatic Distribution

• Organ tropism (selection) exists, as certain cancer cells specialize in metastasizing to specific organs.
• The environment of the secondary site could predict metastasis.

Clinical Manifestations of Cancer

• Symptoms vary by location and extent of cancer.
• Early stages are often asymptomatic.

Local Effects

• Disrupts tissue integrity and function.
• Can produce destructive enzymes and toxins.
• Effusion (fluid buildup) near serous membranes is common.

Pain

• Usually absent in early stages.
• Common in advanced cancer.
• Caused by pressure, obstruction, invasion, stretching of visceral surfaces, infections, inflammation, or tissue death.

Fatigue

• A common cancer symptom.
• Can be caused by the cancer or treatment.

Cachexia

• Severe malnutrition, loss of fat and muscle, and a common cause of cancer-related death.
• Includes anorexia, early satiety, taste alterations, weight loss, anemia, asthenia, and increased infection risk.

Anemia

• Caused by chronic bleeding, malnutrition, bone marrow impairment, or therapy.

Leukopenia, Thrombocytopenia

• Reduced white blood cell and platelet counts, increasing the risk of infection.

Infection

• A significant cancer complication.
• Increased risk due to weakened immunity, malnutrition, and treatment.

Paraneoplastic Syndromes

• Manifestations in areas not directly affected by the cancer.
• Cancer cells may produce hormones or other substances with systemic effects.

Cancer Screening and Treatment

• Early identification improves cancer outcomes.
• Screening includes observation, palpation, imaging, blood tests, and cytologic/histologic methods.

Surgery

• Surgery in cancer management involves diagnosis, prevention, treatment, and palliation.

Radiation

• High-energy radiation precisely targets tumor tissue.
• Damages DNA to kill cancer cells.

Chemotherapy

• Systemic treatment for widespread, rapidly growing tumors.
• Uses cytotoxic drugs that target critically important cellular machinery/ pathways.

Side Effects of Chemotherapy and Radiotherapy

• Rapidly dividing cells are the primary targets, potentially affecting bone marrow, the gastrointestinal tract, hair, skin, and the reproductive system.