Pathophysiology of tumor growth – tumor metabolism, relationship between the tumor and the immune system, paraneoplastic syndrome.
1 Warburg effect (aerobic glycolysis)
Tumor cells preferentially use glycolysis to generate energy even in the presence of oxygen (aerobic glycolysis).
Advantages to tumor cells:
- Provides metabolic intermediates needed for rapid cell growth (nucleotides, amino acids, lipids).
- Acidifies microenvironment (lactic acid production) → promotes invasion and immune evasion.
Diagnostic relevance:
- Basis for PET scans (increased uptake of glucose analog fluorodeoxyglucose [FDG]).
2 Increased glucose uptake
Overexpression of glucose transporters (e.g., GLUT1).
Enhanced hexokinase activity traps glucose inside the cells.
3 Abnormal mitochondrial function
Reduced oxidative phosphorylation.
Resistance to apoptosis.
4 Altered anabolic metabolism
Increased protein, lipid, and nucleotide synthesis to support continuous proliferation.
Relationship Between Tumor and the Immune System
The immune system continuously monitors and eliminates emerging transformed cells (cancer immunoediting).
Evidence:
- Increased cancer incidence in immunodeficient patients.
- Tumor-infiltrating lymphocytes (TILs) correlate with better prognosis.
Mechanisms of immune recognition
Tumor-specific antigens: Unique to tumor cells (e.g., mutated oncogenes).
Tumor-associated antigens: Overexpressed or aberrantly expressed normal proteins.
Mechanisms of tumor immune evasion
Loss or downregulation of MHC class I molecules → reduced cytotoxic T cell recognition.
Secretion of immunosuppressive cytokines (e.g., TGF-β, IL-10).
Expression of immune checkpoint molecules (e.g., PD-L1) → inhibit T cell activation.
Induction of regulatory T cells (Tregs) → suppress anti- tumor response.
Therapeutic implications
Development of immunotherapies:
- Immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1/PD-L1).
- CAR-T cell therapy.
- Cancer vaccines.
Paraneoplastic Syndromes
Definition
Symptom complexes in cancer patients not directly related to tumor invasion or metastasis.
Caused by ectopic hormone production or immune cross-reactivity.
Clinical importance
May be the first manifestation of an occult tumor.
Can mimic metastatic disease.
Important for early diagnosis and management.