The hunt for cancer-initiating cells: a history stemming from leukemia

Conventional cancer therapies are plagued by disease relapses due to incomplete eradication of cancer-initiating cells. Evidence for cancer-initiating cells originally arose from studies in hematology and leukemia. Lessons learned from hematopoietic stem cells laid the bedrock for understanding how leukemic cells self-renew and remain in immature states. Decades later, leukemia-initiating cell techniques are now being applied to the field of solid tumors such as brain, breast, bone, colon, pancreas, lung and prostate cancer, with several cancer-initiating cell efforts led by hematologists. Different isolation techniques enriching for primitive cancer-initiating cells have been developed and are described in this review. Although the concept of cancer-initiating cells arose from studies in normal tissue stem cells, differences exist between neoplastic-initiating clones and their normal counterparts. Several efforts have uncovered aberrant molecular pathways and niche interactions unique to cancer-initiating cells. Efforts to exploit these pathways and interactions could ultimately lead to complete eradication of cancers.