Research Roundup: March 13, 2020

Reading cancer recurrence in the blood, mapping bacterial neighborhoods in the gut, and revealing how a new cancer drug actually works

Kelly Davidson
Credit: Kelly Davidson

Welcome to the March 13, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

An early warning of metastatic cancer

In Clinical Cancer Research, a team led by Viktor Adalsteinsson, associate director of the Gerstner Center for Cancer Diagnostics and group leader for the Blood Biopsy Team in the Cancer Program, and Heather Parsons, a medical oncologist at Dana-Farber Cancer Institute and associated scientist at Broad, reports that personalized blood biopsies demonstrate potential as a tool to detect cancer recurrence earlier than traditional approaches would. The researchers hunted for tumor DNA in banked blood samples from breast cancer patients who had been diagnosed, treated, and monitored for disease recurrence over the last 13 years. The team detected cancer DNA in patient blood samples collected an average of 18 months, and up to three years, before the patients were clinically diagnosed with metastatic recurrence. Learn more in a Broad news story.

Versatile tool to map gut-bacteria neighborhoods 

A complex microbiota inhabits various microenvironments of the gut. Some symbiotic bacteria live in small numbers within these environments, but have a large effect on host physiology. Reporting in Nature Microbiology, Infectious Disease and Microbiome Program’s visiting scientist Wen-Chi Chou, group leader Abby Manson, research scientist Alex Melnikov, senior group leader and institute scientist Ashlee Earl, their Caltech collaborators, and colleagues used a method they called hybrid selection RNA-Seq to boost, by orders of magnitude, the amount of bacterial RNA they could detect from host-rich samples from mice. This technique revealed genes key for bacterial residency within gut neighborhoods and offers a versatile tool for fine mapping bug lifestyles within hosts. Learn more in this Caltech press release and a tweetorial

Cancer-killing complex, clarified

The small molecule DNMDP induces cancer cell death not by leveraging cancer cell dependencies, but through a gain-of-function mechanism involving the formation of a complex between phosphodiesterase 3A (PDE3A) and schlafen family member 12 (SLFN12). Xiaoyun Wu, Heidi Greulich, and colleagues in the laboratory of institute member Matthew Meyerson and at Bayer Pharmaceuticals defined the genomic determinants of cancer cell response to DNMDP, finding DNMDP sensitivity correlated with PDE3A protein levels, and expression of SLFN12 and the aryl hydrocarbon receptor interacting protein are required. Appearing in the Journal of Biological Chemistry, this work clarifies which cancer cells will respond to DNMDP.

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