Module 2: Understanding Cancer Metastasis
A deep dive into the complex process of cancer metastasis, from molecular mechanisms to clinical applications and therapeutic strategies.
Morbidity and Mortality in Cancer Metastasis
How cancer hurts and kills patients
Stephen Paget's landmark 1889 analysis of 735 fatal breast cancer cases revealed that metastatic patterns are not random but follow specific organ preferences. This "seed and soil" hypothesis fundamentally changed our understanding of cancer spread and the mechanisms of cancer-related death.
Key Insights:
- •Metastasis is responsible for 90% of cancer deaths
- •Cancer "poisons" like TNF-α contribute to systemic toxicity
- •Cachexia affects 80% of terminal cancer patients
- •Thrombosis follows Virchow's triad in cancer patients
- •Organ-specific metastasis patterns determine clinical outcomes
📊 Stephen Paget's Analysis (1889)
Analyzed 735 fatal cases of breast cancer and demonstrated that metastatic patterns do not simply follow blood flow distribution, but rather depend on organ-specific factors.
"When a plant goes to seed, its seed is carried in all directions, but they can only live and grow if they fall on congenial soil."
Cancer-Specific Metastatic Patterns
Breast Cancer
Common Sites: Bone, Liver, Lung, Brain
Mechanisms: CXCR4/CXCL12 signaling, Osteomimicry, VEGF expression
Survival Impact: Bone metastases: 2-3 years median survival
Lung Cancer
Common Sites: Brain, Liver, Bone, Adrenal glands
Mechanisms: Blood-brain barrier penetration, Hepatic tropism, Osteolytic factors
Survival Impact: Brain metastases: 4-6 months median survival
Prostate Cancer
Common Sites: Bone, Lymph nodes, Liver
Mechanisms: Osteoblastic factors, PSA signaling, Androgen receptor pathways
Survival Impact: Bone metastases: 1-3 years median survival
Colorectal Cancer
Common Sites: Liver, Lung, Peritoneum
Mechanisms: Portal circulation, CEA signaling, Peritoneal seeding
Survival Impact: Liver metastases: 6-20 months median survival
🎯 Key Takeaways
Clinical Reality
- • Metastasis causes 90% of cancer deaths
- • Most deaths from poison syndromes, not organ failure
- • Cachexia present in 80% of terminal patients
- • 20% of patients develop life-threatening clots
Treatment Challenges
- • No effective cachexia treatments
- • Pain management has severe side effects
- • Thrombosis treated reactively
- • Need for better supportive care