Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015).

INTRODUCTION: Cancer stem cells (CSCs) mediate tumor initiation and maintenance. These cells are chemoresistant and possess characteristics such as self-renewal, pluripotency, plasticity and differentiation. They have aberrant or altered signaling pathways depending on tumor microenvironment, tumor type, etc. CSCs are responsible for highly aggressive and invasive form of the disease following chemo- and/or radiotherapy. Eliminating CSCs is likely to improve the survival rate in patients. Several anti-CSC strategies and associated targets have been proposed and validated till date. Areas covered: The main emphasis is on the patent applications/patents filed/granted in the last few years (2012-2015). The anti-CSC agents are discussed under two broad headings - small- and macromolecules. Different subclasses are further elaborated, e.g., kinase inhibitors, polypeptides, etc. Expert opinion: Clinical development of small- and macromolecular anti-CSC therapeutics is underway. Few of these agents act on validated targets such as kinases. Potential problems with these agents can be envisaged based on our understanding of target biology. Other issues governing the choice of small- versus macromolecules include druggability of the target, ease of its modulation and the presence of compensatory mechanisms. Drug repurposing can be attempted to discover newer anti-CSC drugs quickly.