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Chromosomal instability predicted favorable chemoradiation response in rectal adenocarcinoma
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Errors in chromosomal segregation were linked to improved response to chemoradiation therapy among patients with locally advanced rectal adenocarcinoma, according to study results.
“Persistent chromosome segregation errors represent a conspicuous feature of human neoplasms,” the researchers wrote. “It is widely accepted that this chromosomal instability is associated with poor prognosis; however, its effect on therapeutic response is a matter of conjecture. The results of the current study demonstrate that chromosomal instability is a favorable predictor of response to chemoradiation therapy in patients with locally invasive rectal adenocarcinoma.”
Researchers evaluated pretreatment samples for chromosome mis-segregation and mis-segregation frequency from 62 patients.
They found pathological response to chemoradiation therapy improved among patients with pretreatment errors in chromosome segregation (OR=3.9; P=.02).
Tumor response to treatment was inversely correlated with the frequency of cells with chromosomal errors during anaphase (r=0.94; P˂.05).
Response further improved with simultaneously increased chromosome mis-segregation and decreased levels of Mre11, the DNA damage repair protein (OR=54; P=.008).
“The authors propose that downstream structural damage to chromosomes resulting from segregation errors potentiates the effect of DNA-damaging therapies and synergizes with deficiencies in the DNA repair machinery,” the researchers wrote. “This work identifies a novel mechanistic marker that foretells treatment response to chemoradiation therapy and suggests that concomitant targeting of whole-chromosome segregation and DNA repair may constitute an effective therapeutic strategy.”
Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.
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