Scientist focuses on DNA damage control to pursue new prevention, treatment options
A novel approach to detecting and targeting flaws in first line of defense against cancer has earned an Era of Hope Scholar Award from the U.S. Department of Defense for a scientist at The University of Texas M. D. Anderson Cancer Center.
The award, one of only three given nationally, provides $3.5 million over five years to Shiaw-Yih Lin, Ph.D., associate professor in M. D. Anderson's Department of Systems Biology, to study early defects that lead to breast cancer. The awards support outstanding early-career scientists with high potential for innovation in breast cancer.
Lin's research focuses on the DNA damage response, which detects defects in dividing cells and either repairs them, destroys the cell or deprives it of its ability to divide. The grant funds will be used to explore a crucial component of that process called replication stress response or RSR.
"When cells begin to proliferate very rapidly due to activation of cancer-causing genes or the loss of tumor-suppressor genes, the replication stress response detects that change and blocks these cells from replicating," Lin said. "Genetic defects or flawed proteins in the replication stress response allow precancerous or cancerous cells to bypass this important blockade."
Defects in the RSR pathway occur very early in a normal cell's transition to a cancerous state. "There are no biomarkers for early detection of these defects," Lin said. "We believe we can identify biomarkers that will detect premalignant cells, allowing us to target those cells before they become fully malignant and providing an avenue for preventing breast cancer as well as treating existing disease."
Lin and colleagues plan to characterize the genes involved in the RSR pathway, identify the genetic signature and membrane proteins associated with defective RSR, identify drugs that target the defects, and then develop targeted nanoparticles for diagnostic imaging, prevention and treatment of breast cancer.
There are more than 100 genes involved in the replication stress response. Lin says his team will use state-of-the-art technology to narrow the field to the top five candidates.
The concept of targeting the RSR pathway in cancer research, the scope of the project and its ambition to go from biomarkers to potential treatments in five years, made it an ideal fit for an Era of Hope award.
"One of the key points in the Era of Hope Scholar Award is to select outstanding scientists who are willing to do high-risk, high-yield studies in addition to the incremental science we do that moves us ahead but moves us ahead slowly," said Gordon Mills, M.D., Ph.D., professor and chair of the department of Systems Biology. "These high-risk, high-yield projects are extremely difficult to fund by conventional mechanisms.
"This Era of Hope Scholar Award to Dr. Lin will allow him to take the brand new approach that he's developed and begin to understand a new process of DNA repair, DNA stress and potentially how we can target this," Mills said. "With Dr. Lin's approach, we might be able to help a whole new set of breast cancer patients who do not benefit from current therapies".
The award is part of the 2009 Breast Cancer Research Program administered by the U.S. Army Medical Research and Materiel Command Congressionally Directed Medical Research Programs.
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