What proportion of cells in a malignant neoplasm have the potential to proliferate extensively: all cells, most of them, or only a small minority? This fundamentally important question has direct implications for clinical practice. Which cancer cells need to be killed to cure patients? It is critical both for cancer biologists and for investigators who are seeking to develop new treatments for cancer to know exactly which cells drive cancer growth.
Traditionally, it has been thought that more or less all cells in a malignant neoplasm have a similar potential to proliferate, propagating the disease in a stochastic (random) manner (Figure, A). This theory led to the development of “hatchet” treatments, ie, surgery, radiation therapy, and cytotoxic agents, that sought to eliminate every cell in a malignant neoplasm. Such treatments are of course effective if they eliminate every cancer cell, albeit at the cost of collateral damage to normal tissues. However, when cancers evade early detection or spread early in their development, the hope of killing every cell with a hatchet approach diminishes. This problem is compounded in cancers such as melanoma that are notoriously resistant to conventional systemic therapies.