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Cancer progression is driven in part by genomic alterations1. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations2, leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies3,4. Although DNA sequencing has been implemented in practice, it remains unclear how to use its results. A total of 1,462 patients with HER2-non-overexpressing metastatic breast cancer were enroled to receive genomic profiling in the SAFIR02-BREAST trial. Two hundred and thirty-eight of these patients were randomized in two trials (nos. NCT02299999 and NCT03386162) comparing the efficacy of maintenance treatment5with a targeted therapy matched to genomic alteration. Targeted therapies matched to genomics improves progression-free survival when genomic alterations are classified as level I/II according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)6(adjusted hazards ratio (HR): 0.41, 90% confidence interval (CI): 0.27–0.61, P< 0.001), but not when alterations are unselected using ESCAT (adjusted HR: 0.77, 95% CI: 0.56–1.06, P= 0.109). No improvement in progression-free survival was observed in the targeted therapies arm (unadjusted HR: 1.15, 95% CI: 0.76–1.75) for patients presenting with ESCAT alteration beyond level I/II. Patients with germline BRCA1/2mutations (n= 49) derived high benefit from olaparib (gBRCA1: HR = 0.36, 90% CI: 0.14–0.89; gBRCA2: HR = 0.37, 90% CI: 0.17–0.78). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic breast cancer.

Alzheimer’s disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aβ to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating—Sum of Boxes and Mini Mental State Examination scores. The main safety and tolerability findings are amyloid-related imaging abnormalities. These results justify further development of aducanumab for the treatment of AD. Should the slowing of clinical decline be confirmed in ongoing phase 3 clinical trials, it would provide compelling support for the amyloid hypothesis.

Letter to the Editor

T lymphocytes in culture synthesize and secrete a variety of factors1–6that activate and guide the differentiation3,4, replication5and maturation5of haematopoietic cells in vitro. Malignant T-cell lines as well as T-cell hybridomas producing several of these factors have been established5–13. We report here a factor produced by a human cell line that exerts a potent inhibitory effect on the growth of bone marrow progenitor cells. The properties of this factor, which we have termed colony-inhibiting lymphokine (CIL), differ from other inhibitors of haematopoietic progenitor cell proliferation, but resemble those of a T-cell-derived factor causally linked with some cases of severe aplastic anaemia in humans14. Sensitivity of cells to this factor appears to correlate positively with expression of HLA-DR surface antigens.

AFTERthe results obtained during the gyro-interaction investigations of 1946 and 1947 1, the Istituto Elettrotecnico Nazionale G. Ferraris of Turin and the Institute of Technical Physics of the University of Naples, in association with the Italian Navy, Air Force, Army, Vatican Radio and R.A.I., carried out during May 12–June 8 a third series of experiments in order to measure the depths of parasitic modulation obtained using a disturbing wave the frequency of which was equal to the local gyro-frequency.