Mps1 inhibitors synergise with low doses of taxanes in promoting tumour cell death by enhancement of errors in cell division.
作者： Ana Rita R. Maia , Simon Linder , Ji-Ying Song , Chantal Vaarting , Ute Boon
DOI: 10.1038/S41416-018-0081-2
关键词:
摘要: Chromosomal instability (CIN) is a common trait of cancer characterised by the continuous gain and loss chromosomes during mitosis. Excessive levels CIN can suppress tumour growth, providing possible therapeutic strategy. The Mps1/TTK kinase has been one prime targets to explore this concept, indeed Mps1 inhibitors synergise with spindle poison docetaxel in inhibiting growth tumours mice. To investigate how combination inhibitor (Cpd-5) promote cell death, we treated mice transplanted BRCA1−/−;TP53−/− mammary and/or Cpd-5. were analysed regarding their histopathology, chromosome segregation errors, copy number variations death understand mechanism action drug combination. enhanced efficacy combining an clinically relevant doses associated increase multipolar anaphases, aberrant nuclear morphologies death. Tumours Cpd-5 displayed more genomic deviations, indicating that stability affected mostly combinatorial treatment. Our study shows synergy between taxanes depends on increased errors division, allowing further optimisation treatment regimen for therapy.
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