The blind is off: Moderna COVID-19 vaccine study update

Amidst the tumult in the nation’s capital, a quieter reckoning was taking place this week for the Moderna COVID-19 vaccine clinical trial. Lab Land has been hearing from Emory-affiliated study participants that they’re finding out whether they received active vaccine or placebo. For example, Emory and Grady physician Kimberly Manning, who had written about her participation in the Moderna study in a Lancet essay, posted on Twitter Tuesday. She discovered she had received placebo, and Read more

Combo approach vs drug-resistant fungus

David Weiss and colleagues have identified a combination of existing antifungal drugs with enhanced activity against C. auris when used together. Read more

Fixing Humpty Dumpty in cancer cells

Restoring protein-protein interactions disrupted by an oncogenic mutation is like putting Humpty Dumpty back together Read more

colorectal cancer

Fixing Humpty Dumpty in cancer cells

As Star Trek’s Spock once observed: “As a matter of cosmic history, it has always been easier to destroy than to create.”

The same is true inside human cells, explaining why Emory researchers’ recent accomplishment – finding a small-molecule compound that corrects a defective protein-protein interaction – is so significant for cancer research. It’s like putting Humpty Dumpty back together again.

Xiulei Mo, Haian Fu and colleagues have identified what they call a “mutation-directed molecular glue”. The glue restores a regulatory circuit that when defective, is responsible for acceleration of colorectal and pancreatic cancer. The results are reported in Cell Chemical Biology.

Restoring protein-protein interactions disrupted by an oncogenic mutation is like putting Humpty Dumpty back together again

“It is very exciting, because this is a clear example of a protein-protein interaction stabilizer that can reactivate the lost function and reestablish tumor-suppressive activity,” says Fu, who is chair of Emory’s Pharmacology and Chemical Biology department and leader of Winship Cancer Institute’s Discovery & Developmental Therapeutics program.

Scientists are very good at finding inhibitors for enzymes that are overactive. But they have meager results as far as strengthening interactions that are weak or absent. There are existing examples of drugs that stabilize protein-protein interactions (transplant drugs rapamycin and cyclosporine), but they inhibit the function of the proteins they target, as intended.

Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Aspirin may aid colorectal cancer survival

This week’s Journal of the American Medical Association (JAMA) reports on the potential benefits of aspirin following a colorectal cancer diagnosis.

Dr. Vincent Yang

Vincent Yang, MD, PhD

Emory digestive disease expert Vincent W. Yang, MD, PhD, professor and director of the Division of Digestive Diseases, Emory School of Medicine, comments on the new study:

A large body of evidence shows that regular aspirin use can reduce the formation of colorectal cancer. Aspirin inhibits the activity of an enzyme called cyclooxygenase-2, or COX-2, that is often over-expressed in colorectal cancer.

In the Aug. 12 issue of JAMA, a study led by Andrew Chan, MD, MPH, of the Harvard Medical School, shows that regular aspirin use reduces deaths in patients who had been diagnosed with colon cancer. The study includes two large, diverse groups of individuals who were followed for more than 20 years for various health-related issues.

The individuals who developed colorectal cancer during the follow–up period and had used aspirin regularly had a lower death rate than those patients who developed colon cancers and did not take aspirin. More importantly, the benefit patients received from regularly using aspirin was more apparent if their cancers were positive for COX-2.

The results of this new study are consistent with the earlier finding reported in medical journals about aspirin’s chemopreventive effect on colorectal cancer. However, it should be noted that this study is observational by nature and that regular aspirin use can result in significant toxicities.

To learn more about the routine use of aspirin as an adjunct treatment for colorectal cancer, studies that are blinded and randomized placebo-controlled are necessary. Such clinical trials have been conducted which proved that aspirin taken at 81 mg or 325 mg per day is effective in preventing the recurrence of colorectal adenomas (polyps) after they are removed during screening colonoscopy.

A similar clinical trial could be conducted to test the ability of aspirin to prevent colorectal cancer recurrence. Perhaps patients could first be classified based on the COX-2 levels in their tumors before being randomized into the trial. A potential outcome would be that patients with COX-2-positive tumors would receive more benefit from aspirin use than those with tumors that are COX-2-negative. Chan’s JAMA findings are a catalyst for further study.

Yang is also professor of hematology and oncology at Emory Winship Cancer Institute.

Posted on by admin in Uncategorized Leave a comment