Targeting aneuploid cancer cells

Abstract

Introduction: Most cancers are characterized by some degree of aneuploidy, although its relevance for tumor initiation or progression and the nature of the initial trigger are still not well understood. It was Theodor Boveri who first suggested a link between aneuploidy and cancer at the beginning of the last century, but it is only recently that the molecular mechanisms involved have started to be uncovered.

Areas covered: The molecular mechanisms that are at the origin of aneuploidy and their cellular consequences. Based on these new findings molecular targets have emerged which could lead to a specific treatment of at least some types of aneuploid tumors.

Expert opinion: Therapeutic intervention specifically for aneuploid cells is a very promising approach, however, although new promising targets have been spotted they still need to be tested for proof of concept. Targeting the spindle checkpoint could be an interesting approach for cancer therapy, however, as for other mitotic targets, the open question of the therapeutic window and sensitivity of normal hemopoietic cells has to be considered carefully. Future challenges will not only include identifying and validating druggable targets related to the relevant pathways, but also finding predictive biomarkers to define the responding patient population(s).

Keywords::

• aneuploidy
• cancer
• centrosomes
• mitotic kinases
• spindle assembly checkpoint

Acknowledgements

We thank Susan Watts for helping in revision of the manuscript.

Notes

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