Without a doubt, living cells are extraordinarily complex. They depend on a tangle of delicately balanced, interconnected biochemical reactions, so it’s a wonder they don’t go astray more often, causing cancer or other serious diseases.
The answer lies in the way cells repair themselves and keep themselves running smoothly. Despite getting pelted by damaging toxins, pollutants and even cosmic radiation, cells can rely on damage control systems that quickly fix their cellular dents and scratches and set things right.
This is particularly important when DNA, the root instructions for all cell processes, is involved. Cells need to repair their DNA if it becomes damaged; their survival depends on it. But ironically, DNA repair poses a problem when treating cancer — because harming cancer cells’ DNA is a key to many treatments.
|Researcher Yuan Chen is grappling with SUMO proteins. (Photo by Paula Myers)|
“Radiation and many chemotherapy agents damage DNA; that’s how they kill cancer cells,” said Yuan Chen, Ph.D., professor of immunology at City of Hope. “Unfortunately, as patients receive a number of courses of treatment, their cancer cells often become resistant to DNA damage.” The resistant cancer cells then begin to grow again, and the disease returns.
Chen recently received a four-year, $1.3 million grant from the National Institutes of Health to study a family of proteins involved in DNA repair. The research could boost the power of radiation and chemotherapy to kill cancer.
These molecules are called small ubiquitin-like modifier (SUMO) proteins, and they play major roles in many cellular functions, including DNA repair.
Chen believes they may hold the key to overcoming resistance to chemotherapy and radiation, a major challenge in today’s cancer treatment. Often, therapies battle cancer well at first, but then tumors grow resistant to them and cancer returns. Previous work in Chen’s laboratory reinforces the proteins’ potential.
When she blocks SUMO proteins from doing their usual work — binding to other proteins — in cells in the lab, the cells become more vulnerable to DNA damage, she said. Still, scientists must understand SUMO better before they can design specific treatments.
That’s where Chen comes in. She’s devoted much of her research focus to digging deep down into how the proteins work, and how they influence goings-on inside cells.
Scientists know of three different SUMO proteins, and they act as connectors, she explained. They join together important proteins that otherwise might not unite. Once connected, these new proteins may be involved in any number of cell processes, including DNA repair. In the current project, Chen and her colleagues are trying to identify precisely how each SUMO protein is involved in DNA repair and which other proteins they bring together.
Once they find the specific connections, Chen and her colleagues hope to get additional funding to identify or build molecules that block DNA repair during chemotherapy and radiation. These potential drugs would block one of cancer’s escape routes, helping make modern cancer therapies more effective.