The process starts when a carcinogen (chemical, radiation, viruses, or environmental factors) causes irreversible DNA damage or mutations in a normal cell. Functions: Produces mutations in DNA sequence Alters genes controlling cell growth Creates abnormal cellular behavior Damage may affect oncogenes or tumor suppressor genes Examples of initiators: Tobacco smoke chemicals UV radiation Ionizing radiation Viral infections Environmental toxins
Normal cells contain proto-oncogenes that regulate growth and division. Mutations convert them into oncogenes, causing excessive cell proliferation. Functions: Stimulate continuous cell division Increase growth signaling Reduce dependence on external growth factors Common oncogenes: RAS → controls signal transduction pathways MYC → regulates cell proliferation HER2 → promotes cell growth BCR-ABL → causes uncontrolled kinase activity
Tumor suppressor genes normally prevent excessive cell growth and repair DNA damage. Loss of function leads to uncontrolled proliferation. Functions: Regulate cell cycle checkpoints Promote DNA repair Trigger apoptosis if damage is severe Major tumor suppressor genes: TP53 ("guardian of genome") RB1 BRCA1 BRCA2
Cells possess DNA repair systems to maintain genomic stability. Defects lead to accumulation of mutations. Functions: Detect DNA errors Repair damaged DNA strands Maintain genome integrity Important repair mechanisms: Mismatch repair Nucleotide excision repair Base excision repair Double-strand break repair Consequences: Genomic instability Increased mutation rate Cancer progression
Apoptosis is programmed cell death that removes damaged cells. Cancer cells escape this process. Functions: Prevent elimination of abnormal cells Allow survival of mutated cells Promote tumor persistence Important molecules: BCL-2 Caspases
Tumors require blood vessels to obtain nutrients and oxygen. Functions: Supplies oxygen Delivers nutrients Supports tumor growth and metastasis Major angiogenic factor: VEGF
Cancer cells acquire the ability to spread beyond the primary site. Functions: Break extracellular matrix Enter blood and lymphatic systems Colonize distant organs Molecules involved: Matrix metalloproteinases (MMPs) Cell adhesion molecules Integrins
Cancer cells avoid recognition by the immune system. Functions: Escape immune destruction Suppress immune responses Enhance tumor survival Important immune checkpoint molecules: PD-1 PD-L1 CTLA-4 Simplified Flow Diagram Normal Cell ↓ Exposure to Carcinogen ↓ DNA Damage / Mutation ↓ Oncogene Activation + Tumor Suppressor Loss ↓ Defective DNA Repair ↓ Uncontrolled Cell Division ↓ Apoptosis Avoidance ↓ Angiogenesis ↓ Tumor Formation ↓ Invasion and Metastasis This molecular progression explains how normal cells gradually acquire the characteristics known as the “hallmarks of cancer,” leading to malignant transformation.
