Cancer Mechanisms, Epidemiology, and Treatment

Title: Cancer: Mechanisms, Epidemiology, and Treatment Subject: Oncology Table of Contents 1. Neoplastic Diseases 2. Cancers & Common Types 3. Hallmarks of Cancer 4. Genetic Basis & Mutations 5. Epidemiology & Carcinogens 6. Early Detection & Screening 7. Chemotherapy & Cell Cycle 8. Drug Classes & Mechanisms 9. Adjunctive Agents & Supportive Therapy 1. Neoplastic Diseases Definition: An abnormal mass of tissue resulting when cells divide excessively or fail to die when they should. 2. Cancers & Common Types Definition: Abnormal, disordered, and uncontrolled growth of cells. The affected tissue/cell type defines individual cancers. They can: - Originate in a single tissue type - Grow locally - Spread to distant organs (metastases) Most Common Cancers: - Epithelial: Carcinomas - Mesoderm: Sarcomas - Glandular: Adenocarcinomas 3. Hallmarks of Cancer • Autonomy from growth signals • Evasion of growth inhibition • Unlimited replication (telomere maintenance) • Invasion and metastases • Angiogenesis • Evasion of cell death (apoptosis) Enabled by: Inflammation, genomic instability, and mutations. 4. Genetic Basis & Mutations Clonal Disease: Single cell mutates → dominant cell type → may acquire further mutations → potential chemo resistance. 1 Two-Hit Hypothesis: - First hit: inherited defective tumor suppressor gene - Second hit: acquired mutation in normal allele Germ-line Mutations: Present in sperm/egg; heritable. Differentiation: - Well-differentiated: resemble normal tissue, slower growth - Poorly differentiated: immature, aggressive, poor prognosis Proto-oncogenes → Oncogenes: Mutations produce hyperactive proteins. Tumor Suppressor Genes: Loss-of-function mutations → uncontrolled growth. 5. Epidemiology & Carcinogens Factors: Environmental, reproductive, diet, alcohol, smoking, carcinogens Types of Carcinogens: - Radiation (UV, ionizing) - Chemical (polycyclic hydrocarbons, aromatic amines, etc.) - Infections (HPV, HIV, EBV, H. pylori) Non-modifiable Factors: Inherited genetic predisposition. 6. Early Detection & Screening Definition: Identifying apparently healthy individuals at higher risk. HPV Vaccine: Prevents cervical cancer, offered to girls 12–13. 7. Chemotherapy & Cell Cycle Cell Cycle Phases: - G0: Resting phase, refractory to chemo - G1: Protein/RNA synthesis - S: DNA replication - G2: RNA/protein synthesis continues - M: Cell division Drug Classification: - Phase-specific: affect certain cell cycle phases - Phase-non-specific: affect all phases except G0 - Cycle-non-specific: affect all phases including G0 Growth Fraction: Higher fraction → more chemo-sensitive. Necrotic Centre: Dead cells due to low nutrients. Hypoxic Centre: Low nutrient supply, resistant initially to chemo. Outer Layer: Active division, accessible to chemo. Log Kill Hypothesis: Chemo kills constant proportion per dose; multiple doses reduce cell population progressively. 8. Drug Classes & Mechanisms Alkylating Agents & Platins: Cross-link DNA, causing strand breaks. Ex: Cisplatin, Carboplatin, Oxaliplatin. 2 Antimetabolites: Interfere with nucleoside inclusion; purine/pyrimidine analogs, methotrexate (folate antagonist). Plant Alkaloids & Topoisomerase Inhibitors: - Vinca-alkaloids: Block mitotic spindle (Vincristine) Topoisomerase I inhibitors (Irinotecan, Topotecan) - Topoisomerase II inhibitors (Etoposide) Anthracyclines / Anti-tumor Antibiotics: Intercalation and free radical-induced DNA breaks (Daunorubicin). Asparaginase: Depletes asparagine needed by some cancer cells. Interferons: Immunomodulators, anti-proliferative. Hormonal Therapy: - Glucocorticoids: lympholytic - Tamoxifen: blocks estrogen in breast cancer - GnRH agonists: reduce sex hormones - Aromatase inhibitors: block estrogen production Monoclonal Antibodies: Target tumor-specific receptors, can carry drugs/radiation. 9. Adjunctive Agents & Supportive Therapy Folinic Acid: Enhances fluorouracil effect, mitigates methotrexate toxicity. Fluorouracil: Anti-cancer effects enhanced with folinic acid. Methotrexate: Folic acid antagonist; toxicity reversible with folinic acid. Capecitabine: Prodrug of fluorouracil. MENSA: Protects against urothelial toxicity of ifosfamide/cyclophosphamide. End of Notes 3