Tracking clonal evolution during treatment in ovarian cancer using cell-free DNA
Drug resistance is the major cause of death from ovarian cancer. Why this occurs is problematic and varies with individuals. This study looks at the evolving genetic mutations which cause previously effective chemo to lose its ability to control the cancer.
Using new sequence genetic profiling of circulating tumour DNA, this prospective study followed the course of disease for 18 women with ovarian cancer from diagnosis to recurrence. The main finding was that the genetic clones which disabled the chemo response were present at diagnosis for all these women. This suggests that evolutional preselection is occurring, whereby the environment of chemo promotes the increase in effectiveness of harmful genetic clones.
The authors suggest that understanding this evolutionary effect should lead to a change in management, alter the environment, and prevent the preselection. It seems that drug resistance is due to selective expansion of a small set of genetic clones with reduction of normal clone diversity. Early detection would allow personalisation of chemotherapy.
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