--- module: 040-01 language: en chapter: 40 title: "Cancer Biology, Invasion, Metastasis, and Treatment Principles" module_title: "Foundations" source_sha256: e71131deaaf2e2d6385713b6092f76d5c637fc376fb7f035c51c1602752f1e5f --- # Cancer biology and treatment foundations ## Clonal evolution and drivers ### Cancer as clonal evolution within tissue #### Not simply rapid growth ### Proto-oncogenes activated by mutation, amplification, fusion ### Tumour suppressors: both copies often lost ### DNA-repair defects raise mutation rate #### Characteristic genomic signatures ### Passengers accumulate without major advantage ### Subclones with different vulnerabilities #### Treatment selects resistant populations #### New mutations and plasticity continue evolution ### Germline variants confer predisposition #### Implications for relatives, surveillance, therapy #### Tumour-only finding needs counselling and testing ## Hallmarks of malignancy ### Sustained proliferation, evaded suppression, resisted death ### Genomic instability and inflammation enable traits ### No hallmark unique; combination and persistence ### Autonomous growth signalling ### Checkpoint loss lets damaged cells divide ### Telomere maintenance prevents crisis ### Other death and stress pathways remain targets ### Metabolism supports biomass, redox, hypoxic survival ## Carcinogens and prevention ### Direct DNA damage or metabolic activation ### Ultraviolet lesions; ionising radiation breaks ### Dose, tissue, repair, age, latency shape risk ### Oncogenic infections #### Microbial proteins, inflammation, immune suppression #### Vaccination and antimicrobial treatment prevent ### Risk is probabilistic #### Avoid blame; social and commercial determinants ## Microenvironment and angiogenesis ### Stroma supports or restrains by context ### Hypoxia stabilises pro-tumour programmes #### Angiogenesis, glycolysis, invasion, resistance ### Abnormal, leaky vessels #### Resources but uneven perfusion ### Anti-angiogenic therapy #### Hypertension, thrombosis, bleeding, proteinuria #### Escape via alternative vessels or existing vessels ## Invasion and metastasis ### Breach basement membrane, invade stroma ### Epithelial-mesenchymal programmes add plasticity #### Not one irreversible switch ### Enter vessels, survive, arrest, exit, adapt ### Most disseminated cells fail #### Dormancy for years before outgrowth ### Nodes reflect spread, not sequential passage ### Tissue-specific patterns #### Portal drainage to liver, systemic to lung ## Immune surveillance and escape ### Dendritic cells, T cells, natural killer cells ### Escape: antigen loss, checkpoint ligands, exclusion ### Checkpoint inhibitors release T-cell brakes #### Biomarkers enrich probability but are imperfect ### Immune toxicity in almost any organ #### Early recognition, graded immunosuppression ## Naming, grading, staging, diagnosis ### Benign tumours can secrete, bleed, compress ### Carcinoma in situ: no basement-membrane invasion ### Grade approximates aggressiveness ### Stage describes anatomical extent ### Tissue establishes diagnosis #### Biopsy preserves planes, yields enough tissue ### Predictive, prognostic, monitoring markers #### Tumour markers rarely diagnose alone ## Surgery and radiation ### Surgery: margins and nodes, preserve function ### Neoadjuvant shrinks or tests biology ### Adjuvant eradicates microscopic disease ### Radiation damages DNA directly and via radicals #### Fractionation lets normal tissue repair ### Toxicity: acute inflammatory or late fibrotic ## Systemic and cellular therapy ### Cytotoxics preferentially hit dividing cells #### Marrow, mucosa, follicles, gonads injured ### Combinations attack different pathways ### Targeted agents inhibit specific dependencies ### Antibodies and antibody-drug conjugates ### Endocrine therapy deprives hormone signals ### Resistance: mutation, bypass, lineage change #### Repeat tissue or circulating DNA guides therapy ### Transplant and engineered immune cells #### Cytokine release, neurotoxicity, infection ## Supportive care and survivorship ### Supportive care prevents symptoms and toxicity ### Fertility discussion before gonadotoxic therapy ### Palliative care alongside treatment ### Emergencies: treat threat while confirming cause ### Screening only when benefit exceeds harms ### Survivorship plans for recurrence and late effects