Research ArticleCancer

Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer

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Science Translational Medicine  07 Jun 2017:
Vol. 9, Issue 393, eaal4922
DOI: 10.1126/scitranslmed.aal4922

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Bringing out the neoantigens

Immune checkpoint inhibitors are becoming increasingly popular and successful for the treatment of cancer, but they have not gained much ground in breast cancer so far. Tumors with high mutation rates resulting in more neoantigens should be particularly susceptible to immunotherapy, but even breast cancers with mutations in BRCA1, a DNA repair gene, have thus far not been found to be overly responsive to checkpoint inhibition alone. Nolan et al. found, however, that these tumors may be susceptible to treatment if pushed enough. By treating BRCA1-mutant breast cancers with cisplatin to increase their mutational load and then combining drugs targeting two different immune checkpoint inhibitors, the authors achieved promising results in mouse models, suggesting that a similar approach may also work for patients.

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