Cancer: From Normal Cells to Malignant Tumors

Review of Normal Cells

• Cell: Functional and structural unit, varies in differentiation/specialization.

• Normal Cell Growth: Organized in tissues, differentiated; specialized functions lost with disorganization or uncontrolled growth.

• Cell Structure: Plasma membrane (semipermeable, maintains shape), cytoplasm (nutrients, organelles like ribosomes, mitochondria, lysosomes, Golgi complex), nucleus (DNA, genetic material).

• Cell Communication: Via chemicals or protein channels.

• Cell Adhesion: Mechanisms to maintain tissue organization.

• Cell Cycle: Growth and reproduction (mitosis) controlled by regulator genes, growth factors, and inhibitors.

• DNA: Controls cell function and structure; mutation passed to daughter cells.

• Cell Lifespan: Varies; highly specialized cells (neurons) don't undergo mitosis but have long lifespans; epithelial cells replicate rapidly.

• Cell Reproduction Requirements: Adequate blood supply, nutrients (amino acids, glucose, oxygen).

• Cellular Aging: Natural process with altered structure, decreased function, cell death (apoptosis).

• DNA Alterations: Can mutate spontaneously or due to chemicals, viruses, radiation; may lead to uncontrolled mitosis or cell death.

Benign and Malignant Tumors

• Neoplasm (Tumor): Uncontrolled cellular growth, deprives other cells of nutrients, often atypical/immature cells.

  • Nomenclature: Root indicates cell origin (e.g., chondro for cartilage); suffix -oma for benign, -carcinoma (epithelial) or -sarcoma (connective) for malignant.

  • Oncology: Study of malignant tumors (cancer).

Benign Tumors

• Cells: Similar to normal, differentiated.

• Growth: Relatively slow, expanding mass, often encapsulated.

• Spread: Remains localized; does not spread.

• Damage: Due to compression of adjacent structures.

• Life-threatening: Only in critical locations (e.g., brain).

Malignant Tumors (Cancer)

• Cells: Varied size/shape, large nuclei, undifferentiated, abnormal/increased mitosis.

• Growth: Rapid, infiltrative, not encapsulated, loss of cellular connections.

• Spread: Infiltrates nearby tissues or metastasizes to distant sites via blood/lymph.

• Pathophysiology: Loss of normal organization, growth inhibition, contact controls, altered cell membranes.

  • Compresses blood vessels, causing necrosis and inflammation.

  • Cells secrete enzymes (e.g., collagenase) facilitating spread.

  • Progressive reduction in organ function.

  • Angiogenesis (new capillary development) promoted by some cancer cells.

  • Nutrient trapping deprives normal cells.

  • In situ: Preinvasive stage of cancer, early detection opportunity.

• Grading: Based on degree of differentiation (Grade I: well-differentiated; Grade IV: undifferentiated).

Effects of Malignant Tumors

Warning Signs of Cancer

• Unusual bleeding/discharge.

• Change in bowel/bladder habits.

• Change in wart/mole.

• Non-healing sore.

• Unexplained weight loss.

• Anemia/persistent fatigue.

• Persistent cough/hoarseness.

• Painless solid lump.

Local Effects

• Pain: Usually late symptom; caused by pressure on nerves, stretching visceral capsules, inflammation. May be secondary to infection, ischemia, bleeding.

• Obstruction: Tumor compresses or grows inside passageways (e.g., digestive tract, blood/lymph flow), leading to ulceration, edema, blocked airflow/nerve conduction.

• Tissue Necrosis & Ulceration: Leads to infection (opportunistic flora), particularly in areas like the oral cavity; reduced host resistance.

Systemic Effects (General)

• Weight Loss & Cachexia: Due to anorexia, fatigue, pain, stress, nutrient trapping, altered metabolism, cachectic factors.

• Anemia: From anorexia, chronic bleeding, bone marrow depression.

• Severe Fatigue: Due to inflammatory changes, cachexia, anemia, stress, treatment.

• Infections: Increased susceptibility as host resistance declines.

• Bleeding: Tumor erosion of blood vessels, tissue ulceration, poor clotting (bone marrow depression, hypoproteinemia).

• Paraneoplastic Syndromes: Tumor cells release substances affecting neurologic function, blood clotting, or hormonal balance (e.g., ACTH production by bronchogenic carcinoma causing Cushing syndrome).

Diagnostic Tests

• Blood Tests: Indicate general problems (e.g., low Hb, RBC), monitor treatment effects; cell characteristics diagnostic in leukemias.

• Tumor Markers: Substances (enzymes, antigens, hormones) produced by neoplastic cells; used for screening, diagnosis confirmation, monitoring (e.g., Carcinoembryonic antigen for colon cancer, PSA for prostate cancer).

• Imaging: X-ray, ultrasound, MRI, CT scans to examine tissue changes.

• Cytologic Tests (Biopsy): Only definitive confirmation of malignancy; evaluates tissue biopsies or sloughed cells (e.g., Pap test).

• Genomic Tumor Assessment: Identifies non-hereditary genetic mutations specific to the disease.

Spread of Malignant Tumors

• Invasion: Local spread into adjacent tissue by loosely attached tumor cells secreting lytic enzymes.

• Metastasis: Spread to distant sites via blood or lymphatic channels, forming secondary tumors.

  • Common in regional lymph nodes first; common secondary sites: lungs, liver.

• Seeding: Spread of cancer cells within body fluids or along membranes in body cavities (e.g., ovarian cancer in peritoneal cavity).

Staging of Cancer

• Classification Process: TNM system describes extent of disease for treatment and prognosis.

  • T: Size of primary tumor.

  • N: Extent of regional lymph node involvement.

  • M: Presence of metastasis.

• Stages: Stage I (small, localized, good prognosis) to Stage IV (advanced, multiple sites, poor prognosis).

Etiology (Carcinogenesis)

• Carcinogenesis: Process of normal cells transforming into cancer cells.

• Stages:

  1. Initiating factors (Procarcinogens): Cause first irreversible DNA changes (mutation) due to genetics or environmental risks.

  2. Promoters: Cause further DNA changes, less differentiation, increased mitosis; leads to tumor development (e.g., hormones, environmental chemicals).

  3. Malignant Tumor: Continued exposure/DNA changes lead to growth and local invasion.

  4. Metastasis: Changes in growth regulation enable cells to detach and spread.

• Risk Factors (Carcinogens):

  • Genetic Factors: Oncogenes, tumor-suppressor genes (e.g., breast cancer, retinoblastoma).

  • Viruses: Oncogenic viruses alter host DNA (e.g., HPV for cervical cancer, hepatitis for hepatic cancer, HIV for Kaposi sarcoma).

  • Radiation: Ultraviolet rays, X-rays, gamma rays cause cumulative chromosomal damage (e.g., sun exposure for skin cancer).

  • Chemicals: Exposure to natural/synthetic products (e.g., asbestos/nickel for lung cancer, benzene for leukemia).

  • Biologic Factors: Chronic irritation/inflammation with increased mitosis (e.g., ulcerative colitis for colon cancer).

  • Age: Increasing age.

  • Diet: High-fat diet, smoked foods.

  • Hormones: Estrogen (endometrial cancer).

• Prevention: Limiting sun exposure, regular screenings, diet changes (e.g., increased fiber, antioxidants).

Host Defenses

• Cancer Suppressor Genes: Inhibit neoplastic growth.

• Immune System: Cell-mediated and humoral immunity (cytotoxic T lymphocytes, NK cells, macrophages) react to abnormal tumor cell membranes.

• Immunodeficiency: Increases cancer risk (e.g., HIV/AIDS patients frequently develop Kaposi sarcoma, lymphomas).

Treatment

• Basic Measures: Surgery, chemotherapy, immunotherapy, radiation, or combinations.

• Curative: For small, localized tumors.

• Palliative: For advanced cancer, to reduce manifestations, prolong life.

• Adjuvant Therapy: Prophylactic treatment for micrometastases (undetected secondary tumors).

• Treatment Cycles: Administered in repeated doses with rest periods to maximize tumor cell death and allow normal tissue recovery.

Surgery

• Goal: Removal of tumor and surrounding tissue, including lymph nodes.

• Technique: May use laparoscopy for minimal damage; complete removal sometimes impossible.

• Alternatives: Radiofrequency ablation for small single tumors.

Radiation Therapy

• Mechanism: Causes DNA mutations/alterations, preventing mitosis or causing cell death; damages blood vessels.

• Effectiveness: Most effective on rapidly dividing cells (both tumor and normal). Some cancers are radioresistant.

• Administration:

  • External Sources: Cobalt machine; daily treatments for weeks.

  • Internal Insertion (Brachytherapy): Radioactive materials implanted at tumor site (e.g., cervical, oral, breast cancer).

  • Radioisotope Instillation: In body cavities or orally (e.g., $^{131}I$ for thyroid cancer).

• Adverse Effects: Depend on dose/penetration; damages rapidly reproducing normal cells.

  • Bone Marrow Depression: Most serious; decreased leukocytes (infection risk), platelets (bleeding risk), erythrocytes (fatigue, tissue breakdown). Requires monitoring, transfusions, or treatment postponement.

  • Epithelial Cell Damage: Vasculitis, skin inflammation (sunburn-like), alopecia (hair loss), digestive tract mucosal damage (nausea, vomiting, diarrhea, malnutrition, dehydration, bleeding, stomatitis).

  • Reproductive Organ Damage: Sterility, teratogenesis risk.

  • Nonspecific Effects: Fatigue, lethargy, mental depression.

  • Long-term Effects: Inflammation, necrosis, scar tissue (adhesions, obstruction).

Chemotherapy

• Mechanism: Antineoplastic drugs interfere with protein synthesis and DNA replication at different points in the tumor cell cycle.

• Effectiveness: Most effective against rapidly reproducing cells and small tumor masses.

• Protocols: Combinations of $2-4$ drugs from different classifications (antimitotics, antimetabolites, alkylating agents, antibiotics) administered intravenously; chosen based on tumor cell cycle.

• Adverse Effects: Similar to radiation, damages normal rapidly reproducing cells.

  • Bone Marrow Depression: Limiting factor; dangerously low blood counts (leukopenia, neutropenia, thrombocytopenia, anemia). Major risks: hemorrhage, infection.

  • Vomiting: Direct chemical stimulation of emetic center, mucosal inflammation; can be anticipatory.

  • Epithelial Cell Damage: Alopecia, skin/mucosa breakdown (stomatitis, diarrhea, candidal infections).

  • Unique Damaging Effects: Fibrosis in lungs, myocardial damage depending on drug.

Other Drugs

• Hormones (e.g., Prednisone): Decrease mitosis, increase erythrocyte counts, improve appetite, reduce inflammation/swelling.

• Sex Hormones/Blocking Agents: Beneficial if tumor growth is hormone-dependent (e.g., estrogens for prostate cancer, tamoxifen for estrogen-dependent breast cancer).

• Biologic Response Modifiers: Augment immune response (e.g., interferon, BCG vaccine).

• Targeted Therapies: Drugs targeting molecular pathways or receptors (e.g., trastuzumab for breast cancer, antibody-labeled radioisotopes for lymphoma).

• Angiogenesis Inhibitors (e.g., Bevacizumab): Block new blood vessel growth to starve tumors. Effect on chemotherapy delivery is a concern.

• Analgesics: Pain control, stepwise approach from mild to strong narcotics (e.g., morphine).

Gene Therapy

• Experimental Treatment: Replace mutated genes, inactivate mutated genes, introduce new genes.

Nutrition

• Challenges: Malnutrition common due to taste changes, anorexia, vomiting, sore mouth, pain, fatigue, malabsorption, altered metabolism, nutrient trapping.

• Measures: Ice/mouth rinses, frequent small meals of nonirritating favorite foods, pain control, antiemetics, total parenteral nutrition if needed.

Complementary Therapies

• Nonmedical therapies; no research-based evidence to prolong life or reduce metastasis alone, but may offer hope.

Prognosis

• Cure: Generally defined as $5$-year survival without recurrence.

• Factors: Early diagnosis and treatment improve prognosis.

• Variability: Death rates vary greatly by cancer type; some (e.g., lung cancer) have poor prognosis, others (e.g., childhood leukemias, Hodgkin lymphoma) have improved survival rates.

Examples of Malignant Tumors

Skin Cancer (Basal Cell Carcinoma)

• Prognosis: Excellent (visible, easily diagnosed/treated, slow-growing).

• Characteristics: Pearly papule with central ulceration, painless, persistent, slowly invasive.

• Risk Factors: Sun exposure, fair skin, older age.

Ovarian Cancer

• Prognosis: Very poor (hidden, silent tumor, rapid growth, early spread).

• Signs: Vague, appear late (altered bowel/bladder function, increased abdominal girth).

• Spread: Easily via lymphatic vessels and seeding along peritoneal membranes to liver/other organs.

Brain Cancer

• Prognosis: Serious (space-occupying masses, pressure inside skull).

• Location Impact: Tumors in brain stem/cerebellum can interfere with vital functions.

• Spread: Malignant brain tumors typically do not metastasize outside CNS; however, secondary tumors can metastasize into the brain from other primary sites (breast, lung, bone).

• Early Indications: Seizures, headache, drowsiness, vomiting, visual problems, impaired motor function.