--- module: 040-02 language: en chapter: 40 title: "Cancer Biology, Invasion, Metastasis, and Treatment Principles" module_title: "Tumour evolution, biomarker reasoning, treatment resistance, and oncological emergencies" source_sha256: 9dd97be25818d857591f1fd8fdbd46cc015f5a6402825a80730a882909845058 --- # Tumour evolution, biomarkers, resistance, emergencies ## Tumour evolution ### Evolving ecosystem, not uniform mass #### Descendants gain genetic, epigenetic, phenotypic change #### Hypoxia, immunity, treatment select variants ### Biopsy samples one region at one time #### Metastasis or relapse clone may differ ### Drivers create dependencies ### Repair loss gives predictive patterns #### Mismatch-repair instability, defective recombination ### Pathogenic label not proof of active driver #### Allele fraction, copy number, clonality, context ## Stress tolerance and metabolism ### Telomeres, checkpoint evasion, apoptosis resistance ### Metabolism supplies nucleotides, lipids, reducing power ### Aerobic glycolysis diverts carbon into biomass ### Dependence on a nutrient or repair pathway #### Therapeutic window ### Normal proliferating tissues share needs #### Marrow, mucosal, hair, gonadal toxicity ## Microenvironment ### Fibroblasts stiffen matrix, restrict access ### Macrophages kill or support tumour by signals ### Hypoxia selects acidosis-tolerant cells ### Abnormal vessels leak, shunt, collapse #### Uneven drug delivery #### Sanctuaries for resistant cells ## Invasion, metastasis, dormancy ### Loss of polarity and adhesion, motility ### Each metastatic step inefficient ### Pre-metastatic niche prepared before arrival ### Tropism reflects circulation and compatibility ### Dormant cells reactivate after years #### Surgery cannot prove microscopic absence #### Adjuvant therapy when risk justifies toxicity ### Neoadjuvant shrinks and reveals sensitivity #### Progression on therapy exposes resistance ## Immunity and immune toxicity ### Immunity constrains and shapes cancer #### Selection favours antigen loss and exclusion ### Checkpoint blockade restores existing T cells #### Durable only if antigen, presentation, trafficking ### Immune-related events during or after treatment #### Grade promptly, exclude infection and progression #### Steroids matched to severity #### Hormone deficiency may be permanent ### Mild symptoms do not prove organ safety #### Myocarditis, pneumonitis, adrenal crisis fatal #### Treat instability without waiting ### Prolonged steroids: prophylaxis, glucose, bone ## Tissue diagnosis ### Representative tissue obtained safely #### Avoid contaminating planes, fracture, seeding ### Core tissue preserves architecture ### Cytology may exhaust material ### Fixation and decalcification impair assays ### Pre-biopsy: coagulation, antithrombotics, bleeding ### Image-guided viable margin, not necrotic centre ### Lymphoma: preserve architecture ### Sarcoma: route allowing en bloc excision ## Grade, markers, and response ### Grade, stage, molecular subtype are distinct ### Prognostic versus predictive markers #### Association does not prove targeting helps ### Treatment can enlarge lesions without progression ### Stable size may hide biological response ### Markers vary with inflammation and clearance #### Low-risk marker screening causes overdiagnosis ## Local and cytotoxic therapy ### Surgery cures if all clonogenic disease removed #### Margins depend on biology and anatomy ### Node assessment risks lymphoedema, nerve injury ### Fractionation exploits repair and reoxygenation ### Late fibrosis and second cancers years later ### Combinations reduce resistant clone survival #### Overlapping toxicity constrains dose ### Vesicant extravasation needs immediate care ## Targeted and endocrine therapy ### Works only when target present and necessary ### Resistance pre-exists or emerges #### Target mutation, bypass, transformation ### Targeted means selection, not harmlessness ### Progression: check adherence, pseudoprogression #### Few sites escaped: add local treatment #### Negative liquid biopsy not proof of absence ### Endocrine therapy withdraws hormone signals #### Bone loss, insulin resistance, vasomotor effects ## Emergencies and survivorship ### Treat physiology before complete histology ### Cord compression: timed record, full spine imaging ### Hypercalcaemia: rehydrate, bridge antiresorptive delay ### Vena-cava obstruction: secure tissue if stable #### Airway or cerebral crisis takes priority ### Palliative care from diagnosis ### Screening only if benefit outweighs harms ### Treatment summary assigns follow-up responsibility