BACKGROUND:
Distant
recurrences after antineoplastic treatment remain a serious problem for breast
cancer clinical management, which threats patients' life. Systemic therapy is
administered to eradicate cancer cells from the organism, both at the site of
the primary tumor and at any other potential location. Despite this intervention,
a significant proportion of breast cancer patients relapse even many years
after their primary tumor has been successfully treated according to current
clinical standards, evidencing the existence of a chemoresistant cell
subpopulation originating from the primary tumor.
METHODS/FINDINGS:
To
identify key molecules and signaling pathways which drive breast cancer
chemoresistance we performed gene expression analysis before and after
anthracycline and taxane-based chemotherapy and compared the results between
different histopathological response groups (good-, mid- and bad-response),
established according to the Miller & Payne grading system. Two cohorts of
33 and 73 breast cancer patients receiving neoadjuvant chemotherapy were
recruited for whole-genome expression analysis and validation assay,
respectively. Identified genes were subjected to a bioinformatic analysis in
order to ascertain the molecular function of the proteins they encode and the
signaling in which they participate. High throughput technologies identified 65
gene sequences which were over-expressed in all groups (P ≤ 0·05 Bonferroni
test). Notably we found that, after chemotherapy, a significant proportion of
these genes were over-expressed in the good responders group, making their tumors
indistinguishable from those of the bad responders in their expression profile
(P ≤ 0.05 Benjamini-Hochgerg`s method).
CONCLUSIONS:
These data
identify a set of key molecular pathways selectively up-regulated in
post-chemotherapy cancer cells, which may become appropriate targets for the
development of future directed therapies against breast cancer.
Source: Transcriptional
shift identifies a set of genes driving breast cancer chemoresistance. Vera-Ramirez L, Sanchez-Rovira P, Ramirez-Tortosa CL,
Quiles JL, Ramirez-Tortosa M, Lorente JA (laura.vera@genyo.es).
PLoS
One. 2013;8(1):e53983.
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