From Nautil.us, October 5:
A medicine that disrupts the DNA replication of cancer cells may be within reach.
Himanshu Brahmbhatt was staring at the results of a clinical trial that looked too good to be true. A co-founder and CEO of EnGeneIC, a biopharmaceutical company, Brahmbhatt was running a small trial that was testing a fundamentally different approach to fighting cancer. Patients in the group had grim prospects. They had exhausted all other options. With nothing left to lose and not expecting any miracles, they enrolled in the trial. They wanted to give it one more chance. Now their scans showed their tumors had stopped progressing. Even more remarkable was they didn’t have the same type of tumors. They had malignancies affecting different organs—lungs, bladders, colons, pancreases—and yet, they uniformly did well.
“These people were facing death,” Brahmbhatt says. “Then we started seeing that they were actually succeeding. You could see in the scan that the tumor has stopped growing. It was a feeling of such extreme internal joy that it’s very difficult to describe.”
The results may have appeared miraculous, but they were anything but. They stemmed from fundamental research into cell division that forms the basis of the EnGeneIC process. A longtime advisor to the company, Bruce Stillman, professor of biochemistry and president and CEO of Cold Spring Harbor Laboratory, has been studying the process of DNA replication, which plays a key role in cell division and cancer progression.
“Cancer cells multiply out of control,” says Stillman, who has devoted his career to studying DNA replication. “When a cell becomes a cancer cell, the very first thing that happens is the cells begin to divide without the normal controls. And the first thing that has to happen before the cell has to divide into two daughter cells is to copy the genome. So, the path that leads to cancer is in part dysregulation of the process that controls DNA replication.” The abnormal DNA replication causes the accumulation of mutations in the genome that advances cancer. Interfering with the process of cell division has long been a focus for treating cancer, but because normal cell division is unavoidably affected also, many of these chemotherapies are toxic. EnGeneIC has figured out a way around this problem by combining a novel method of drug delivery with a way to stop DNA replication.
Stillman was a graduate student when he understood that cell division, and DNA replication in particular, were key targets for treating cancer. That insight inspired him to switch careers from medicine to medical research. At the time, the science of DNA was a burgeoning field and there was a lot to discover; Stillman was a pioneer. He uncovered many of the mysteries of the genome replication process and what sets the copy machinery in motion. He has spent 40 years putting together the pieces of the molecular puzzle. “I wanted to understand how this process really works,” he says. And he did.
Deep inside the tens of trillions of cells that comprise your body, the DNA replication machinery is constantly speeding along in many tissues. In the bone marrow alone, 500 million red and white blood cells are produced every minute. There’s about two meters of DNA in each cell, neatly woven inside the nucleus. To keep the blood cell supply steady, about a billion meters of DNA must be copied every minute. “You could wrap that around the Earth along the equator about 25 times,” Stillman says. It is inevitable that over the course of a person’s lifetime, this process will make mistakes—some harmless, but others leading to malignant mutations. So, understanding the cogs of this complex machinery may hold the key to combating many cancers.....
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