More NMDA but less excitotoxicity? Now possible

Many researchers have wanted to enhance NMDA receptor signals to treat disorders such as schizophrenia. But at the same time, they need to avoid killing neurons with “excitotoxicity”, which comes from excess calcium entering the Read more

Update on pancreatic cancer: images and clinical trial

In 2018, Winship magazine had a feature story on pancreatic cancer. Our team developed an illustration that we hoped could convey the tumors’ complex structure, which contributes to making them difficult to treat. Oncologist Bassel El-Rayes described how the tumors recruit other cells to form a protective shell. "If you look at a tumor from the pancreas, you will see small nests of cells embedded in scar tissue," he says. "The cancer uses this scar Read more

New animal model for elimination of latent TB

An animal model could help researchers develop shorter courses of treatment for latent Read more

Sumin Kang

Overcoming cisplatin resistance

Despite being studied for decades, the chemotherapy drug cisplatin is revealing new aspects of how it works. Researchers at Winship Cancer Institute of Emory University have identified an enzyme responsible for making tumors and cancer cell lines resistant to cisplatin, along with an experimental drug that targets that enzyme.

The results were published on July 19 in Cancer Cell.

Winship researcher Sumin Kang, PhD

Cisplatin is a DNA-damaging agent used in standard treatment for lung, head and neck, ovarian, and testicular cancers. It has a simple structure, grabbing DNA with its metallic (platinum) arms to form crosslinks. It used to be known as “cis-flatten” because of its nausea-inducing side effects. The experimental drug, lestaurtinib, has already been tested in clinical studies in combination with other chemotherapy drugs, which means it could easily go into trials against tumors displaying cisplatin resistance.

Sumin Kang, PhD, and colleagues at Winship decided to look for enzymes whose activity was necessary for cancer cells to withstand cisplatin treatment. They chose kinases, enzymes that often control some aspect of cell growth and are have plenty of existing drugs targeting them. The researchers found that in combination with a sub-lethal amount of cisplatin, “knocking down” the activity of the kinase MAST1 kills a cell. But how does that combination work?

Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Orange lichens are source for potential anticancer drug

An orange pigment found in lichens and rhubarb called parietin may have potential as an anti-cancer drug, scientists at Winship Cancer Institute of Emory University have discovered.

The results were published in Nature Cell Biology on October 19.

Caloplaca_Fenwick

Parietin, shown to have anticancer activity in the laboratory, is a dominant pigment in Caloplaca lichens. Note: this study did not assess the effects of eating lichens or rhubarb. Photo courtesy of www.aphotofungi.com

Parietin, also known as physcion, could slow the growth of and kill human leukemia cells obtained directly from patients, without obvious toxicity to human blood cells, the authors report. The pigment could also inhibit the growth of human cancer cell lines, derived from lung and head and neck tumors, when grafted into mice.

A team of researchers led by Jing Chen, PhD, discovered the properties of parietin because they were looking for inhibitors for the metabolic enzyme 6PGD (6-phosphogluconate dehydrogenase). 6PGD is part of the pentose phosphate pathway, which supplies cellular building blocks for rapid growth. Researchers have already found 6PGD enzyme activity increased in several types of cancer cells.

“This is part of the Warburg effect, the distortion of cancer cells’ metabolism,” says Chen, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. “We found that 6PGD is an important metabolic branch point in several types of cancer cells.” Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Melanoma mutation rewires cell metabolism

A mutation found in most melanomas rewires cancer cells’ metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

The V600E mutation in the gene B-raf is present in most melanomas, in some cases of colon and thyroid cancer, and in the hairy cell form of leukemia. Existing drugs such as vemurafenib target the V600E mutation — the finding points to potential alternatives or possible strategies for countering resistance. It may also explain why the V600E mutation in particular is so common in melanomas.

Researchers led by Jing Chen and Sumin Kang have found that by promoting ketogenesis, the V600E mutation stimulates production of a chemical, acetoacetate, which amplifies the mutation’s growth-promoting effects. (A feedback mechanism! Screech!)

The results were published Thursday, July 2 in Molecular Cell.

More on this paper here.

Posted on by Quinn Eastman in Cancer 1 Comment