Cancer causes many human deaths worldwide. Much evidence is supporting the idea that human cancers can be considered as a stem cell disorder. Malignant tumour can be viewed as an abnormal organ in which a small population of tumourigenic cancer stem cells have escaped the normal limits of self-renewal giving rise to abnormally differentiated cancer cells that contribute to tumour progression and growth. The cancer-initiating cells or cancer stem cells were originally identified in hematological malignancies but are now being recognised in several solid tumours. Cancer stem cells are reported to show resistance to anticancer drugs and radiotherapy, and therefore, they are involved in progression, recurrence and metastasis of cancers. The statement that only a subset of cells drive tumour formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumuor stem cell population or inducing the differentiation of these cells. Differentiation therapy involves the use of agents, individually or in combination, that can induce differentiation of cancer cells. This approach is based on the concept that cancer cells are transformed cells that have been arrested at an immature or less differentiated state, lack the ability to control their own growth and so multiply at an abnormally fast rate. Although differentiation therapy does not destroy cancer stem cells, it restrains their growth and self-renewal property and finally allows the application of more conventional therapies (such as chemotherapy) to eradicate the malignant cells. In recent years, many new differentiation-inducing agents have been used in the fight against cancer. The first differentiation agent found to be successful was all-trans-retinoic acid (ATRA). ATRA is capable of differentiating a variety of cancer stem cells and stimulates them to change from cancerous cells into mature cells which do not divide. In acute promyelocytic leukemia, ATRA could induce leukemic cell terminal differentiation and hematologic remission in 90% of patients. It has also been shown that retinoic acid can suppress carcinogenesis in a variety of tissues (e.g. skin, lung, breast and oral cancers). Human glioblastomas appear to be established and expanded by cancer stem cells, which are endowed with tumourinitiating and perpetuating ability. Currently, therapeutic drug-induced differentiation by bone morphogenetic proteins and retinoic acid is considered as a promising approach to eradicate stem-like cell population in glioblastomas and thus blocking the tumour growth. Some types of cancer cells are prevented from entering the differentiation pathway partly because of abnormal chromatin modification enzymes, which keep cancer cells in the cycling state. For example, abnormal recruitment of histone deacetylase activity has been associated with the development of definite human cancers. It has been shown that histone deacetylase inhibitors such as suberoylanilidehydroxamic acid and valproicacid, can work as differentiation inducers in cancer cells and have been used experimentally in cancer differentiation therapy. Differentiation agents have less toxicity than conventional cancer treatments and have potential to target the population of stem-like cells in tumours. Here, the application of some effective agents used in differentiation therapy and their mechanism of action in cancer prevention are discussed.

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