Reprogramming cancer cells in endocrine-related tumors: open issues

Reprogramming technologies have been developed to revert somatic differentiated cells into pluripotent stem cells that can be differentiated into different lineages potentially useful in stem cell therapy. Reprogramming methods have been progressively refined to increase their efficiency, to obtain a cell population suitable for differentiation, and to eliminate viral plasmid which could be responsible for many unwanted side-effects when used in personalized medicine. All these methods are aimed to introduce into the cell genes or mRNAs encoding a set of four transcription factors (OCT- 4, SOX-2, KLF-4 and c-MYC) or a set of three lincRNAs (large intragenic non-coding RNAs) acting downstream of the reprogramming transcription factors OCT-4, SOX-2 and NANOG. Translational clinical applications in human pathologies and in developmental, repair and cancer biology have been numerous. Cancer cells can be, at least in principle, reprogrammed into a normal phenotype. This is a recently raised issue, rapidly advancing in many human tumors, especially endocrine-related cancers, such as breast, prostate and ovarian ca. The present review aims to describe basic phenomena observed in reprogramming tumor cells and solid tumors and to discuss their meaning in human hormone-related cancers. We will also discuss the fact that some of the targeted transcription factors are "normally" activated in a number of physiological processes, such as morphogenesis, hypoxia and wound healing, suggesting an in vivo role of reprogramming for development and homeostasis. Finally, we will review concerns and warnings raised for in vivo reprogramming of human tumors and for the use of induced pluripotent stem cells (iPSCs) in human therapy.