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Aptamers are nucleic acid oligomers synthesized from groups of arbitrary oligonucleotides to bind to a wide range of bio-targets with high specificity and high affinity that are comparable to antibodies. In the last decade, label-free electrochemical cancer aptasensors based on biomarker and whole-cell detection have been demonstrated to be highly sensitive, faster, and more stable than typical clinical techniques. Compared to optical aptasensors, label-free electrochemical aptasensors are promising lab-on-chip candidates for portable clinical applications since their sample preparation procedure is relatively simple, and their signals can be easily digitized. In order to enhance the performance of aptasensors, it is crucial to have a deep understanding of the sensing mechanisms of different types as well as their key advantages and disadvantages. This review discusses some of the features of two major groups of cancer aptasensors—optical and electrochemical—before moving on to a detailed discussion of state of the art, and technical challenges and opportunities associated with label-free electrochemical cancer aptasensors. Label-free electrochemical cancer aptasensors based on biomarkers and related proteins as well as the ones based on cell detection, are discussed in the relevant sub-sections. The review is concluded with an address of future perspectives.

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