TUMORIGENESIS
Tumorigenesis is a multistep genetic process in which normal cells acquire progressive genetic and epigenetic alterations, leading to uncontrolled proliferation, survival advantage, invasion, and metastasis.
Cancer is fundamentally a genetic disease of somatic cells, caused by accumulation of mutations that affect genes regulating:
- cell cycle,
- apoptosis,
- DNA repair,
- cell differentiation,
- cell–cell interaction.
II. GENERAL CELLULAR AND MOLECULAR CHARACTERISTICS OF THE CANCER CELL
Cancer cells show a characteristic set of biological properties, often referred to as the hallmarks of cancer.
Key Cellular Characteristics
Cancer cells differ from normal cells by:
- autonomous growth signaling,
- resistance to growth inhibition,
- evasion of apoptosis,
- unlimited replicative potential,
- genomic instability,
- ability to invade and metastasize.
Molecular Characteristics
- Persistent activation of growth-promoting pathways.
- Inactivation of growth-inhibitory mechanisms.
- Defects in DNA repair → accumulation of mutations.
- Altered metabolism (aerobic glycolysis – Warburg effect).
- Ability to induce angiogenesis.
- Immune evasion.
III. DRIVER AND PASSENGER MUTATIONS
- Driver mutations are genetic alterations that directly contribute to tumor initiation and progression by providing a selective growth advantage.
- Passenger mutations are biologically neutral mutations that accumulate during cell division but do not contribute to cancer development.
Characteristics of Driver Mutations
- Affect genes controlling proliferation, apoptosis, or genome integrity.
- Are positively selected during tumor evolution.
- Usually involve oncogenes or tumor suppressor genes.
- A limited number of driver mutations is sufficient to initiate cancer.