The paradox of cancer cell apoptosis.

Resistance to apoptosis is an accepted property of human cancer cells and resistance to cancer therapy is often considered to involve increased resistance to apoptosis. However, comparison of the potential doubling times of human tumour cells with the volume doubling times of the tumour from which they are derived implies a high rate of apoptosis. For at least some cancer types, increased proliferation rate and correspondingly increased apoptosis is associated with a poor prognosis. How can resistance to apoptosis and apoptosis be reconciled? One possible resolution of this paradox is that at least two tumour cell populations are involved, a smaller, more rapidly growing population with self-renewal properties and resistance to apoptosis, and a larger, more slowly growing population that is susceptible to apoptosis. The progeny of smaller population thus maintains the larger population. This review describes the evidence for such a model and its implications for cancer therapy.