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Jusino et al. J Cancer Metastasis Treat 2018;4:43 I http://dx.doi.org/10.20517/2394-4722.2018.24 Page 13 of 20

amplification in tumor initiation, maintenance, progression, and chemo/radio-resistance through intra-
tumor heterogeneity. One mechanism shows that centrosome amplification results in multipolar or
pseudobipolar mitotic spindles that may culminate in aneuploidy and chromosome instability, thus
contributing to intra-tumor heterogeneity. The other mechanism shows how defects in cytokinesis lead
to tetraploidy and chromosome instability. This mechanism also promotes tumor initiation, maintenance,
progression, and chemoresistance through intra-tumor heterogeneity. The reader should also keep in mind
that centrosome aberrations may contribute to malignant phenotypes in cancer such as invasion through
changes in polarity, and such phenotypes occur independently of chromosome instability.

However, the role of centrosome amplification in tumorigenesis needs to be further elucidated in human
tumors because it has been shown that centrosome aberrations are highly context-dependent and several
other mechanisms may apply . Another aspect that is worth studying in the future is the effect of functional
[202]
centrosome aberrations (microtubule nucleation, disorganized mitotic spindle, etc.) and other structural
centrosome aberrations such as changes in shape, size position, and composition in cancer. Also, clustering
mechanisms and normal spindle bipolarization through extra chromosome inactivation and how these vary
in cancer. Nevertheless, proper classification of centrosome aberrations in human tumors might have a
diagnostic or prognostic value. Therefore, it would be beneficial to explore the therapeutic applications of
chromosome instability in cancer. As reviewed here, chromosome instability inhibitors such as AURKs,
Mps1, and PLKs inhibitors can help improve cancer treatment by preventing centrosome amplification
and chromosome instability. Another strategy will be to increase chromosome instability levels to promote
-
cancer cell death, but this will be context dependent. For example, this strategy can be used for ER breast
cancers, since extreme chromosome instability correlates with better prognosis in patients with this
molecular phenotypes. On the other hand, increasing chromosome instability in ER breast tumors is a poor
+
strategy, since there is a direct relationship between increases in chromosome instability and poor survival.
In addition, increasing chromosome instability may increase chemotherapy resistance in some patients. SCS
can help to address specific genotype that confers cancer cell subpopulations adaptive advantages and impede
complete tumor clearance. The advances in both SCS and the identification of putative therapeutic targets
are promising toward a complete understanding of cancer and how effective treatment can be achieved.

DECLARATIONS
Authors’ contributions
Conceived the general idea of the review and made up the structure: Jusino S, Saavedra HI
Searched the literature and drafted the manuscript: Jusino S, Fernández-Padín FM
Read and approved the final manuscript: all authors

Availability of data and materials
Not applicable.

Financial support and sponsorship
This study was supported by the NIGMS-RISE Training Program (R25GM082406), by PSM-U54-CA163071
and MCC-U54-CA163068 from the National Institutes of Health. The project was also supported by
2U54MD007587 from the PRCTRC, G12MD007579 from RCMI, The Puerto Rico Science, Technology and
Research Trust, and Ponce Medical School Foundation Inc. under the cooperative agreement 2016-00026.
The content is solely the responsibility of the authors and does not necessarily represent the official views of
the National Institutes of Health.

Conflicts of interest
All authors declare that there are no conflicts of interest.