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