• A gene that promotes cell division, differentiation, and survival
• These genes have the potential to cause cancer when mutated

• Mutated version of a proto-oncogene
• The mutation is associated with formation of tumors
• The mutations result in higher expression or over activity of the protein

• These genes restrict (limit) cell division and may promote cell apoptosis
• They are called tumor suppressor genes because mutations that cause low protein expression or loss of function are associated with cancer

• Contact inhibition occurs with normal cells, whereas cancer cells do not respond to cell-cell contact
• Tumors cells tend to produce more growth factors and have exaggerated response to growth factors
• Tumor cells have oncogenes that contribute to carcinogenesis
• Tumor cells have loss of tumor suppressor gene function
• Tumor cells have immortality related to the maintenance of telomere length by the enzyme telomerase

• Initiation
• Promotion
• Transformation
• Progression

• Inactivation of tumor suppressor genes
• Expression of telomerase

In tumor cells, if telomere length is too short, a crisis occurs.  If the cell gains a function by producing telomerase instead of undergoing apoptosis, the cell will continue to divide and become immortalized

• Tumors are genetically heterogeneous (some cells are more resistant to treatment than others)
• Larger tumor size and longer duration of treatment increases probability of resistance
• Just one resistant cell is required

Reduced Intracellular Concentration of Drug

• Inactivation of drug
• Prevent uptake of drug
• Promote efflux of drug

Altered Drug Target

Insensitivity to Apoptosis

Bypass Metabolic Requirement for Target