Journal Watch

Matching therapies to subtypes of EGFR-mutated lung cancer

New research from Vanderbilt investigators suggests that clinicians should take a deeper dive into distinguishing EGFR mutations when prescribing targeted therapies for non-small cell lung cancers. EGFR exon 19 deletion mutations are the most common EGFR mutations in patients with lung cancer. However, the term “exon 19 deletion” is a catch-all phrase used to denote more than 20 distinct EGFR mutations that have different genomic coordinates and different protein structures. Despite these differences, all EGFR exon 19 deletion mutations are currently treated the same in the clinic. Benjamin Brown, PhD, is the lead author of the study published July 22 in Proceedings of the National Academy of Sciences. He is part of an interdisciplinary team from the labs of Jens Meiler, PhD, and Christine Lovly, MD, PhD.

Possible preventive treatment for gastric cancer   

A study published June 11 in Gastroenterology reveals new insights into how gastric cancer develops and suggests a preventive treatment. Eunyoung Choi, PhD, and colleagues identified for the first time that Trop2+/CD133+/CD166+ dysplastic stem cells are a key source of clonal evolution of dysplasia to multiple types of gastric cancer. Their investigation further showed that pyrvinium, a commonly prescribed treatment for intestinal pinworms, blocked regeneration of dysplastic stem cells by controlling the CK1a signaling protein in mouse models and in human organoids.

Potential new target against colorectal cancer 

Researchers have discovered a potential new target in the fight against colorectal cancer, the nation’s third most common malignancy and, next to lung cancer, the second leading cancer killer. R. Daniel Beauchamp, MD, and Anna Means, PhD, and colleagues reported July 18 in Gastroenterology that a cell-signaling protein/chemokine called CCL20 and its receptor, CCR6, are essential to the growth of colorectal tumors following the loss of a tumor suppressor protein, SMAD4. This alphabet soup of proteins appears to hold a key to identifying and ultimately interrupting the complex, multicellular events that spur malignant growth in the colon.

Black patients with cancer have worse COVID outcomes

Black patients with cancer experienced significantly worse outcomes after COVID-19 diagnosis than non-Hispanic white cancer patients in a study published March 28 in JAMA Network Open. Sonya Reid, MD, MPH, and other investigators of the COVID-19 and Cancer Consortium studied the electronic health records of 3,506 patients for the analysis, including data of 1,068 Black patients and 2,438 non-Hispanic white patients. Black patients had a 17% mortality rate 30 days after diagnosis, compared to 13% for non-Hispanic whites. The investigators found that Black patients had worse preexisting comorbidities, severity of COVID-19 at presentation and outcomes. Black patients had worse outcomes even when cancer status and cancer treatments were similar between the two groups.

Ten-second videos predict bloodcancer relapse

Ten-second videos of white blood cell motion in the skin’s microvasculature greatly improved the prediction of which stem cell and bone marrow transplant patients would have a relapse of their blood cancer. In the typical immune response, white blood cells are seen to interact with the inner walls of veins, rolling along them like bowling balls before adhering to them, then exiting through them to go to sites of inflammation. Transplant patients whose white blood cells were caught on video with greater adherence levels and greater rolling along vessel walls were more than three times as likely to have cancer relapse or die, compared to those with normal adherence and rolling levels. The study by Inga Saknite, PhD, Eric Tkaczyk, MD, PhD, and colleagues was reported March 26 in JAMA Dermatology.

C. difficile may contribute to colorectal cancer 

The bacterium Clostridioides difficile (C. difficile), which causes severe diarrhea and an estimated 400,000 infections annually in the United States, may be a previously unrecognized contributor to colorectal cancer. The findings from human colon cancer specimens, cell culture and mouse models were reported Aug. 5 by researchers at Johns Hopkins University and Vanderbilt University Medical Center in the journal Cancer Discovery. Single-cell RNA-sequencing experiments led by Nicholas Markham, MD, PhD, and Ken Lau, PhD, showed that C. difficile brought about a range of changes within colon cells that made the cells vulnerable to more rapid growth and carcinogenic mutations.