The pathogenesis of cancer involves a complex interplay of genetic, environmental, and lifestyle factors leading to the transformation of normal cells into malignant ones.
Key mechanisms and processes include:
1. Genetic Mutations
Oncogenes: Mutations activate genes like RAS and MYC, causing uncontrolled cell proliferation.
Tumor Suppressor Genes: Inactivation of genes like TP53 removes growth restraints.
DNA Repair Genes: Mutations in genes such as BRCA1 and BRCA2 lead to genomic instability.
2. Environmental and Lifestyle Factors
Carcinogens: Substances like tobacco smoke and asbestos cause mutations.
Radiation: UV and ionizing radiation damage DNA.
Infections: Viruses (e.g., HPV, HBV, HCV) and bacteria (e.g., Helicobacter pylori) contribute to cancer.
Diet and Physical Activity: Poor diet, obesity, and lack of exercise increase cancer risk.
3. Epigenetic Changes
DNA Methylation: Aberrant patterns can silence tumor suppressor genes or activate oncogenes.
Histone Modification: Affects gene expression and contributes to carcinogenesis.
Non-coding RNAs: Regulate gene expression and play roles in cancer development.
4. Tumor Microenvironment
Cancer Stem Cells: Self-renewing cells drive tumorigenesis.
Angiogenesis: New blood vessel formation supplies the tumor; VEGF is key.
Immune Evasion: Tumors express proteins like PD-L1 to evade the immune system.
5. Progression and Metastasis
Invasion: Cancer cells degrade the extracellular matrix using enzymes like MMPs.
Metastasis: Spread of cancer cells to distant organs involves detachment, invasion, survival in circulation, and colonization of new sites.
6. Clonal Evolution
Genetic Heterogeneity: Diverse cell populations within tumors drive clonal evolution and therapy resistance.