bims-ovdlit 2022-07-31 papers

Issue of 2022‒07‒31
three papers selected by
Lara Paracchini
Humanitas Research

Lancet Oncol. 2022 Aug;pii: S1470-2045(22)00139-5. [Epub ahead of print]23(8): e374-e384

Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup.

participants of the 6th Gynecologic Cancer InterGroup (GCIG) Ovarian Cancer Consensus Conference on Clinical Research

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer.

DOI: https://doi.org/10.1016/S1470-2045(22)00139-5

Elife. 2022 Jul 27. pii: e71569. [Epub ahead of print]11

Unsupervised detection of fragment length signatures of circulating tumor DNA using non-negative matrix factorization.

Gabriel Renaud, Maibritt Nørgaard, Johan Lindberg, Henrik Grönberg, Bram De Laere, Jørgen Bjerggaard Jensen, Michael Borre, Claus Lindbjerg Andersen, Karina Dalsgaard Sørensen, Lasse Maretty, Søren Besenbacher.

Sequencing of cell-free DNA (cfDNA) is currently being used to detect cancer by searching both for mutational and non-mutational alterations. Recent work has shown that the length distribution of cfDNA fragments from a cancer patient can inform tumor load and type. Here, we propose non-negative matrix factorization (NMF) of fragment length distributions as a novel and completely unsupervised method for studying fragment length patterns in cfDNA. Using shallow whole-genome sequencing (sWGS) of cfDNA from a cohort of patients with metastatic castration-resistant prostate cancer (mCRPC), we demonstrate how NMF accurately infers the true tumor fragment length distribution as an NMF component - and that the sample weights of this component correlate with ctDNA levels (r=0.75). We further demonstrate how using several NMF components enables accurate cancer detection on data from various early stage cancers (AUC=0.96). Finally, we show that NMF, when applied across genomic regions, can be used to discover fragment length signatures associated with open chromatin.

Keywords: cancer biology; genetics; genomics; human

DOI: https://doi.org/10.7554/eLife.71569

Nat Cancer. 2022 Jul;3(7): 793-807

Cancer-associated fibroblasts in the single-cell era.

Dor Lavie, Aviad Ben-Shmuel, Neta Erez, Ruth Scherz-Shouval.

Cancer-associated fibroblasts (CAFs) are central players in the microenvironment of solid tumors, affecting cancer progression and metastasis. CAFs have diverse phenotypes, origins and functions and consist of distinct subpopulations. Recent progress in single-cell RNA-sequencing technologies has enabled detailed characterization of the complexity and heterogeneity of CAF subpopulations in multiple tumor types. In this Review, we discuss the current understanding of CAF subsets and functions as elucidated by single-cell technologies, their functional plasticity, and their emergent shared and organ-specific features that could potentially be harnessed to design better therapeutic strategies for cancer.

DOI: https://doi.org/10.1038/s43018-022-00411-z