ABSTRACT
Ever since the discovery of cancer stem cells (CSCs), they have progressively attracted more attention as a therapeutic target. Like the mythical hydra, this subpopulation of cells seems to contribute to cancer immortality, spawning more cells each time that some components of the cancer cell hierarchy are destroyed. Traditional modalities focusing on cancer treatment have emphasized apoptosis as a route to eliminate the tumor burden. A major problem is that cancer cells are often in varying degrees of dedifferentiation contributing to what is known as the CSCs hierarchy and cells which are known to be resistant to conventional therapy. Differentiation therapy is an experimental therapeutic modality aimed at the conversion of malignant phenotype to a more benign one. Hyperthermia therapy (HT) is a modality exploiting the changes induced in cells by the application of heat produced to aid in cancer therapy. While differentiation therapy has been successfully employed in the treatment of acute myeloid leukemia, it has not been hugely successful for other cancer types. Mounting evidence suggests that hyperthermia therapy may greatly augment the effects of differentiation therapy while simultaneously overcoming many of the hard-to-treat facets of recurrent tumors. This review summarizes the progress made so far in integrating hyperthermia therapy with existing modules of differentiation therapy. The focus is on studies related to the successful application of both hyperthermia and differentiation therapy when used alone or in conjunction for hard-to-treat cancer cell niche with emphasis on combined approaches to target the CSCs hierarchy.
