Cancer
Group of genes could anticipate the response to key breast cancer treatment

New research has identified a genomic signature that makes it possible to anticipate which patients with HR+/HER2- breast cancer will respond less well to CDK4/6 inhibitors.
CDK4/6 inhibitors, combined with hormone therapy, are the standard treatment for this advanced type of breast cancer
The research findings may help personalise therapies and design new combinations.
Dr Eudald Felip, ICO oncologist and postdoctoral researcher at IrsiCaixa, and Dr Edurne Garcia-Vidal, postdoctoral researcher at IrsiCaixa, are first authors of the study.
They explained: “We analysed almost a hundred patients treated at ICO Badalona.
“57 per cent of them had a good response to treatment, with more than two years without progression of the tumour, while the remaining 43 per cent showed an unfavourable evolution, with relapse after a few months.”
When comparing the two groups, researchers found that poorly responding patients had tumours with abnormal immune system activation.
This, far from favouring the fight against the tumour, is associated with an immune environment that helps the cancer to resist treatment.
From this analysis, KIMA (Key Immune Activation) was born, a signature composed of the combined expression of nine genes -including STAT1, FOXP3 and TIGIT- whose high presence predicts a worse evolution of the disease: faster progression and shorter overall survival.
In fact, the mean time to disease progression varies from 11 months in patients with high KIMA presence to 36 months in those with low KIMA presence.
The result was further validated in a second clinical study, which also found that patients who did not respond to CDK4/6 inhibitors had higher levels of KIMA.
Dr. Ester Ballana, is leader of the Virus-Host Interactions (ViHIT) research group at IrsiCaixa, and Dr Mireia Margelí, is oncologist and researcher at ICO and IGTP in the Applied Research Group in Oncology of Badalona (B· ARGO).
The researchers wrote: “What we have seen is that, in this type of cancer, a highly activated immune system does not mean more defence, but more resistance of the tumour.
“This genetic signature allows us to identify these patients early on and opens the door to combining CDK4/6 inhibitors with novel immunomodulatory strategies.”
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