Potential molecular therapeutic targets in cancer stem/progenitor cells: Are ATP-binding cassette membrane transporters appropriate targets to eliminate cancer-initiating cells?

Recent advances in the basic and clinical oncology have revealed that the malignant transformation of the tissue-resident adult stem/progenitor cells into leukemic or tumorigenic cancer stem/progenitor cells plays a central role in the etiopathogenesis and progression of the most human cancers. Cancer stem/progenitor cells endowed with a high self-renewal capacity and aberrant differentiation potential generally possess the high expression levels and activity of diverse ATP-binding cassette (ABC) transporters, DNA repair and detoxifying enzymes and anti-apoptotic factors. These phenotypic and functional features common to the most of cancer stem/progenitor cells have been associated with their intrinsic or acquired resistance phenotype to numerous chemotherapeutic drugs, disease recurrence and poor patient survival. Moreover, the sustained activation of distinct oncogenic signaling elements in these immature cancer-initiating cells during disease progression may also contribute to their acquisition of a more malignant behavior and development of metastatic disease state. Of particular interest, we describe the potential therapeutic targets to eradicate the cancer-initiating cells and their mature progenies in a variety of aggressive human cancers such as leukemias, melanoma and solid tumors including brain and epithelial cancers. The emphasis is on potential therapeutic molecular targets in cancer stem/progenitor cells and their progenies including ABC drug transporters, ceramide, telomerase, and diverse tumorigenic signaling elements.