A cutting-edge solution to a Gordian knot? Aptamers targeting cancer stem cell markers for strategic cancer therapy

Cancer stem cells (CSCs) are key drivers of tumor proliferation and serve as a basis for therapeutic resistance, metastasis, and recurrence. The erratic efficacy of conventional therapeutic approaches is limited because of their inability to exterminate CSCs. This has spurred the development of novel cancer treatment paradigms that target specifically these cells. Importantly, CSCs are identified and classified based on the differential expression of biomarkers, facilitating their precise isolation and tailored therapeutic interventions. Numerous promising approaches have been developed to target CSC markers, paving the way to precision medicine in cancer treatment. Aptamers are molecularly targeting agents comprising single-strand oligonucleotides arranged in a unique fashion that allows them to bind their targets, including cancer biomarkers, with high specificity and affinity. Given their programmable nature, they can be chemically modified and integrated with various diagnostic components, including nanoparticles (NPs), drugs, and therapeutic RNAs, thereby enhancing their applicability in disease treatment. In this review, we shed light on various aptamer designs that show potential to target putative CSC markers and to efficiently deliver therapeutic moieties.