Seven fundamental changes in cell physiology that together determine malignant phenotype.

 Self-sufficiency in growth signals

• Tumors have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation.

 Insensitivity to growth-inhibitory signals

• Tumors may not respond to molecules that are inhibitory to the proliferation of normal cells such as transforming growth factor-? (TGF-?), and direct inhibitors of cyclin-dependent kinases.

 Evasion of apoptosis

• Tumors may be resistant to programmed cell death, as a consequence of inactivation of p53 or other changes.

 Defects in DNA repair

• Tumors may fail to repair DNA damage caused by carcinogens or unregulated cellular proliferation.

 Limitless replicative potential

• Tumor cells have unrestricted proliferative capacity, associated with maintenance of telomere length and function.

 Sustained angiogenesis

• Tumors are not able to grow without formation of a vascular supply, which is induced by various factors, the most important being vascular endothelial growth factor (VEGF).

 Ability to invade and metastasize

• Tumor metastases are the cause of the vast majority of cancer deaths and depend on processes that are intrinsic to the cell or are initiated by signals from the tissue environment.

References

 Robbins pathology