Precision medicine with multiple myeloma

“Precision medicine” is an anti-cancer treatment strategy in which doctors use genetic or other tests to identify vulnerabilities in an individual’s cancer subtype. Winship Cancer Institute researchers have been figuring out how to apply this strategy to multiple myeloma, with respect to one promising drug called venetoclax, in a way that can benefit the most patients. Known commercially as Venclexta, venetoclax is already FDA-approved for some forms of leukemia and lymphoma. Researchers had observed that multiple Read more

Promiscuous protein droplets regulate immune gene activity

Biochemists at Emory are achieving insights into how an important regulator of the immune system switches its function, based on its orientation and local environment. New research demonstrates that the glucocorticoid receptor (or GR) forms droplets or “condensates” that change form, depending on its available partners. The inside of a cell is like a crowded nightclub or party, with enzymes and other proteins searching out prospective partners. The GR is particularly well-connected and promiscuous, and Read more

Neutrophils flood lungs in severe COVID-19

In the lungs of severe COVID-19 patients, neutrophils camp out and release inflammatory cytokines and tissue-damaging Read more

cancer genomics

Mapping the cancer genome wilderness

A huge cancer genome project has highlighted how DNA that doesn’t code for proteins is still important for keeping our cells on track.

The Pan-Cancer Analysis of Whole Genomes analyzed more than 2,600 tumors from 38 tissues, looking for causative mutations and patterns. Previous work had concentrated on the regions of the genome that code for proteins, but a significant proportion of cancer patients’ tumors don’t carry known “driver” (causative) mutations in protein-coding regions. So this project went out into what used to be called “junk DNA” or the “dark matter” of the genome.

Emory bioinformatics postdoc Matthew Reyna is the first author of one of 23 papers on the PCAWG project, published Feb. 5 in the Nature family of journals. His paper in Nature Communications looks at mutations in non-coding regions of the genome in tumors, analyzing which biological processes are affected.

Some of these were mutations in the promoters of genes encoding well-known cancer suppressors such as p53, but the project also identified new genes containing cancer-driving mutations. A promoter is the stretch of DNA that tells the cell “make RNA copies starting here”.

Reyna contributed to the project while he was at Princeton, working with Benjamin Raphael, and at Emory as well. More recently, he’s been investigating protein-protein interactions with Haian Fu, Andrey Ivanov and others as part of the Cancer Target Discovery and Development (CTD2) project.

Posted on by Quinn Eastman in Cancer Leave a comment

Invasive cancer cells marked by distinctive mutations

What does it take to be a leader – of cancer cells?

Adam Marcus and colleagues at Winship Cancer Institute are back, with an analysis of mutations that drive metastatic behavior among groups of lung cancer cells. The findings were published this week on the cover of Journal of Cell Science, and suggest pharmacological strategies to intervene against or prevent metastasis.

Marcus and former graduate student Jessica Konen previously developed a technique for selectively labeling “leader” or “follower” lung cancer cells in culture, using lasers that turn a fluorescent protein from green to red. The leaders are more adventurous and invasive, but the followers support the leaders and help them survive. Check out our prize-winning video and their 2017 Nature Communications paper.

The magenta cells have leader-specific mutated Arp3 protein, while the green cells are unmodified followers.

The new research harnesses their technique to track the mutations that are specific to leader or follower cells. It was a collaboration with the lab of Paula Vertino, formerly at Winship and now at University of Rochester. Cancer Biology graduate students Elizabeth Zoeller and Brian Pedro led the work, with sophisticated genomics from Ben Barwick.

One of the leader-specific mutations was in Arp3, part of a protein complex that promotes the protrusion of cellular blobs, facilitating migration. The researchers took the mutated Arp3 protein from leader cells and forced its production in follower cells. In the cover image, the magenta cells on the outside are the ones with the mutated Arp3 protein, while the green cells are unmodified. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Statins, prostate cancer and mitochondria

In honor of Fathers’ Day, we are examining a connection between two older-male-centric topics: statins and prostate cancer.

Statins are a very widely prescribed class of drugs used to lower cholesterol levels, for the purpose of preventing cardiovascular disease. In cell culture, they appear to kill prostate cancer cells, but the epidemiological evidence is murkier. Statin effects on prostate cancer incidence have been up in the air, but recent reports point to the possibility that starting statins may slow progression, after a man has been diagnosed with prostate cancer.

Winship Cancer Institute researchers have some new results that shed some light on this effect. John Petros, Rebecca Arnold and Qian Sun have found that mutations in mitochondrial DNA make prostate cancer cells resistant to cell death induced by simvastatin [Zocor, the most potent generic statin]. Sun recently presented the results at the American Urological Association meeting in Orlando.

In other forms of cancer such as breast and lung cancer, genomic profiling can determine what DNA mutations are driving cancer growth and what drugs are likely to be effective in fighting the cancer. The prostate cancer field has not reached the same point, partly because prostate cancers are not generally treated with chemotherapy until late in the game, Petros says. But potentially, information on mitochondrial mutations could guide decisions on whether to initiate statin (or another) therapy.

“This is part of our soapbox,” he says. “When we are looking at mutational effects on prostate cancer, let’s be sure to include the mitochondrial genome.”

Winship’s Carlos Moreno and his colleagues are working on the related question of biomarkers that predict prostate cancer progression, after prostatectomy surgery and potentially after just a biopsy.

Read more

Posted on by Quinn Eastman in Cancer Leave a comment