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The tumor suppressor RAD51C is mutated in ovarian cancers. Through variant analysis the authors identify a mutation cluster in the RAD51C Walker B region important for the repair of DNA double-strand breaks and replicative damage. By identifying Walker B separation-of-function alleles, they show that these activities can be uncoupled.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

The identification of biomarkers of response to PARP inhibitors can enable selection of appropriate ovarian cancer patients for treatment. In this study, the authors report clinical results and exploratory biomarker analyses from the ARIEL2 phase 2 clinical trial on the safety and efficacy of the PARP inhibitor rucaparib in patients with recurrent ovarian cancers

Some patients present with multiple lung tumours but it is unclear whether these are metastases or individual lesions. Here, the authors use genomics techniques to demonstrate in six patients that multiple tumours have individual genetic profiles and represent separate tumours.

Granulomatous/sarcoid-like lesions have been reported in patients treated with immune checkpoint inhibitors (ICIs). Here the authors report the occurrence of “nodal immune flare”, an apparent radiological cancer progression in the nodes characterized by the absence of cancer and the presence of non-caseating granulomas, in patients with non-small cell lung cancer following neoadjuvant ICI treatment.

Confocal and multiphoton fluorescence microscopy often suffers from low dynamic range. Here the authors develop a high dynamic range, laser scanning fluorescence technique by simultaneously recording different light intensity ranges. The method can be adapted to commercial systems.

ATR/CHK1 pathway inhibitors represent a therapeutic option for platinum-resistant high-grade serous ovarian carcinoma (HGSOC). Here the authors report the results of a phase 2 clinical study of the CHK1 inhibitor prexasertib in patients with BRCA wild-type platinum-resistant HGSOC with or without biopsiable disease.

The combination of neoadjuvant nivolumab, ipilimumab and chemotherapy showed promising efficacy in patients with resectable non-small cell lung cancer, with higher tumor immune cell infiltration and tertiary lymphoid structures after treatment compared with neoadjuvant nivolumab plus chemotherapy.

Neoadjuvant treatment with nivolumab plus ipilimumab is well tolerated and demonstrates clinical efficacy in patients with early stage lung cancer.

A Phase I/II trial previously revealed variable anti-tumor efficacy of the PARP inhibitor niraparib in combination with the PD-1 inhibitor pembrolizumab in platinum-resistant ovarian cancer patients. Here, the authors perform an integrated genomic and immunomics analysis of tumor samples from the same patients and find potential predictive biomarkers of response to such combination therapy.

Interferon-ε is a tumour suppressor expressed in the epithelial cell of origin of ovarian cancer, which it restricts by direct action on tumour cells and especially by activation of anti-tumour immunity.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

Around 10% of high-grade serous ovarian carcinomas (HGSOC) harbor BRCA1 promoter methylation, but it is uncertain how it predicts response to PARP inhibition. Here, the authors show that homozygous BRCA1 methylation predicts response to rucaparib while heterozygous methylation of BRCA1 predicts resistance in HGSOC.

Surgery and chemotherapy form the cornerstone in the treatment of ovarian cancer. The standard of care for primary ovarian cancer is platinum and taxane-based chemotherapy. Despite the favorable response characteristics, however, most women with advanced-stage ovarian cancer will relapse. Herzog and Pothuri discuss the treatment options available and highlight the issues surrounding how these patients should be managed with surgical, chemotherapy, biological targeted agents and radiation therapy.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

Site-specific hyperphosphorylations of tau in the cerebrospinal fluid change with disease course, and correlate with pathology and cognitive decline in dominantly inherited Alzheimer’s disease.

The Dominantly Inherited Alzheimer Network neuroimaging repository is a free resource consisting of PET and MRI scans from 533 individuals across 206 families who are deeply phenotyped with genetic, clinical, cognitive and biofluid sampling.

Responses to anticancer therapy are hampered by several factors, and Peter S. Nelson and colleagues here identify a protective effect of the tumor microenvironment. After cytotoxic chemotherapy, inflammatory NF-κB signaling activates the secretion of WNT16B, which acts on epithelial cells, promoting their survival and fostering tumor growth in vivo. This pathway is also active in human tumors treated with chemotherapy and illustrates the potential caveats of cyclical therapy and the need to overcome environmental protection to successfully eliminate tumors.

Two new cranial fossils found in Kenya have bearing on the relationship between Homo habilis and Homo erectus. Descriptions of a small H. erectus skull, and jaw material from a late-surviving specimen of Homo habilis demonstrate that the two species co-existed in the Lake Turkana basin in Kenya for almost half a million years.