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Oncology- Cancer Phenotype
I. The Genesis of Cancer:
Cancer cells must acquire several crucial capabilities to survive and thrive. These can be categorized as follows:
Recent research highlights the importance of the tumor microenvironment (stroma) in cancer progression.
I. The Genesis of Cancer:
- Genetic Basis: Cancer arises from the accumulation of DNA mutations. These mutations disrupt normal cellular processes that prevent tumor formation (tumourigenesis).
- Epithelial Origin: Most cancers originate in epithelial tissues (epithelial cancers). Research heavily focuses on why these tissues are susceptible and the protective mechanisms cancer cells evade.
Cancer cells must acquire several crucial capabilities to survive and thrive. These can be categorized as follows:
- Evading Tissue-Specific Controls: In rapidly renewing tissues (like the intestinal epithelium), cancer cells must overcome:
- Cell Sloughing: Escape the normal process of shedding old cells.
- Terminal Differentiation: Avoid the programmed cell death associated with differentiation.
- Generic Capabilities Required for Growth and Survival:
- Immune Evasion: Escape destruction by the immune system.
- Angiogenesis: Develop a new blood supply (necessary for nutrient and oxygen delivery, waste removal).
- Growth Factor Independence: Grow and proliferate even without external growth signals.
- Metabolic Adaptation: Survive under conditions of energetic stress.
- Resistance to Apoptosis (Programmed Cell Death): Avoid signals triggering cell suicide.
- Metastasis:
- Invasion and Intravasation: Invade surrounding tissues and enter the bloodstream or lymphatic system.
- Extravasation and Colonization: Exit the circulation and establish secondary tumors (metastases) at distant sites (e.g., liver).
Recent research highlights the importance of the tumor microenvironment (stroma) in cancer progression.
- Stromal Components: Pancreatic ductal adenocarcinoma exemplifies this, with up to 80% of tumor mass consisting of non-cancerous stromal cells, including:
- Immune cells: (e.g., macrophages)
- Fibroblasts: Connective tissue cells
- Endothelial cells: Blood vessel cells
- Stromal Roles:
- Tumor Growth Support: Stromal cells actively contribute to tumor growth.
- Physical Barrier: They can impede drug penetration, limiting the effectiveness of therapies.
- Survival Factor Provision: They can secrete factors that protect cancer cells from targeted therapies.
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