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Ponnusamy et al. Cancer Drug Resist 2019;2:297-312 I http://dx.doi.org/10.20517/cdr.2018.11 Page 309

FUTURE DIRECTION AND CONCLUSION
Acquired chemoresistance in general involves a broad range of poorly-comprehended domains (genetic-
epigenetic) and different partners that cross-talk within and between domains that underwrite the need
for an integrated approach. Strong body of evidence exists to support the role of epigenetic changes that
contribute to cellular reprogramming (leading to EMT and CSC phenotype) during acquired resistance
development. Though the existing reports support the functional role of EMT and associated signaling
in cancer stemness, the question of whether EMT solely drive stemness to induce chemoresistance in the
face of co-existing genetic-epigenetic landscape remain to be explored. Nevertheless, addressing epigenetic
regulation associated with cellular reprogramming is important in the context of chemo-resistance and
breast cancer treatment. A better understanding of the dynamic epigenetic regulatory network in initiating
and stabilizing the EMT-CSC signaling in breast cancer is needed. This will help designing better therapies
that address not only the genetic changes but also the reversible epigenetic changes during the transient
process of EMT and stemness.

DECLARATIONS
Authors’ contributions
Concepted: Ponnusamy L, Singh KP
Designed: Ponnusamy L, Singh KP
Wrote (first draft): Ponnusamy L
Wrote, reviewed, discussed, edited, and revised: Ponnusamy L, Mahalingaiah PKS, Chang YW, Singh KP

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

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

Ethical approval and consent to participate
Not applicable

Consent for publication
Not applicable

Copyright
© The Author(s) 2019.

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