Annual Report - 2006-2007
Discoveries in the Makingby Eileen A. Ellig
Behind the research benches at M. D. Anderson, there are thousands of investigators — young and seasoned alike — who are determined to unearth the causes of cancer and to translate their findings into new treatment options for patients.
While it’s clearly not a simple task, investigators continue to make fundamental discoveries that are providing “increasing insights into the inner wiring of cancer cells that distinguishes them from normal cells and helps to explain their abnormal behavior,” says Robert C. Bast Jr., M.D., vice president for translational research at M. D. Anderson.
Over the past year, for example, critical factors that regulate tumor cell growth, spread and survival have been identified. One finding suggests that the very building blocks of cells, the nucleotides, may actually promote cancer cell survival by functioning as natural inhibitors of proteins responsible for regulating cell death and, consequently, serve as a barrier that cells must overcome to undergo programmed cell death.
Another study reveals that molecules on the cell surface not only instruct cells to grow, but also travel to the nucleus, or the cell’s core, where they can act on genes and other proteins to regulate cell division and repair. Any disruption in normal cell functioning can lead to disease development. Investigators noted, for instance, that the absence or weak expression of a protein critical to protecting skin cells from harmful mutations leaves the cell’s genes vulnerable to silencing and causes genetic instability.
Still other studies point to specific precancerous genes that, when inactivated, allow early growth of premalignant cells in the development of bladder and, possibly, other cancers.
Basic observations like these are essential for uncovering new targets for therapy. In separate studies, for instance, investigators have learned that a key protein overexpressed in brain tumors and a defective version of a tumor suppressor gene in non-small cell lung cancers may serve as potential biomarkers for determining which chemotherapy agents will be most effective in treating these diseases. Too often, tumors become resistant to therapy by turning on specific survival factors, making them more difficult to treat.
It’s not enough to identify these targets, however. Investigators must then develop methods to target these specific abnormalities, selectively destroying cancer cells. In the past year, various research teams have been busy devising ways to package tumor-killing viruses or corrective genes by either encasing them in tiny balls of fat known as liposomes, or inserting them into nanoparticles (particles so small that they are measured in billionths of a meter).
Of particular note is a preclinical study showing that a molecularly engineered delivery system can selectively embed a gene in pancreatic tumors, leading to the shrinkage or, in some cases, elimination of these cancer cells. Investigators also found that this therapeutic approach can inhibit the spread of disease and prolong survival with virtually no toxicity. They’re planning to test this system in patients in a clinical trial.
While the steady decline in federal funding for cancer research threatens to slow the pace of discovery, M. D. Anderson investigators are pushing forward. With more research grants awarded by the National Cancer Institute than any other academic institution, including 10 NCI-funded Specialized Programs of Research Excellence grants, and research support from all sources totaling approximately $445 million in 2007, they continue to translate their understanding of cells and tissues at the molecular level into better approaches for the diagnosis, detection and treatment of cancer.
“Our goal in research is to understand cancer in sufficient detail so that we can individualize therapy to predict exactly which drugs would be most effective for treating a particular cancer patient’s tumor with the least toxicity,” Bast says. “If we are to realize this goal, we need to work as efficiently and as effectively as possible.”
Full speed ahead.