To many, how cancer manifests itself in the body, what went wrong as those first few errant cells divided, and what can be done to stop cancer’s dangerous migration through the body is an unsolved puzzle. But some people just can’t let puzzles sit unfinished. From Sunday crosswords to carcinomas, Alan Rapraeger, PhD, has been tackling puzzles his whole life.

“Since I was a kid, I’ve loved solving puzzles. I still love it, so here in the research environment, my challenge is to solve puzzles about what a tumor cell is doing and what makes it different from a normal cell,” says Rapraeger, professor of human oncology at the University of Wisconsin School of Medicine and Public Health. “If we can figure out what that is, we can target it with a therapeutic and cure cancer.”

Since I was a kid, I’ve loved solving puzzles. I still love it, so here in the research environment, my challenge is to solve puzzles about what a tumor cell is doing and what makes it different from a normal cell.

Using peptides to attack cancer cells

Rapraeger’s team of scientists works on a family of receptors called syndecans, which help the cell organize other receptors on the cell’s surface.

Syndecans recognize the extracellular matrix, a complex protein structure that surrounds the cell, and bind to these proteins. In this way, cells recognize their surroundings and their neighboring cells and “know where they are.”

Normal breast epithelial cells rely on a number of receptor signals and processes to survive. In tumor cells, those processes can become unregulated and lead to unchecked growth.

Intriguingly, the receptor complexes that are organized by syndecans appear essential for tumor cells. They communicate with the cell, causing it to grow and multiply and even invade other parts of the body, just what tumor cells need to be successful.

“But if we inhibit those complexes on a tumor cell, those cells die. And we can do that simply by introducing a peptide. We can make a peptide that represents the site in the syndecan that organizes these other receptors; it disrupts the receptor complex and deactivates it, and breast tumor cells die,” says Rapraeger.

“We can treat normal breast cells with high amounts of these peptides, and the normal cells are fine.”

Tiny cells offer exciting potential for therapies

Work at the sub-cellular level may seem very small and specialized, but it’s actually a large area of study for Rapraeger’s lab to explore.

“Each person has something different to work on. We’re all excited about our research. We get together and have meetings and lab discussions and everybody’s wondering what happened since we last talked about the experiments. That interaction cuts across the floor. Here on the third floor of WIMR I (Wisconsin Institutes for Medical Research), a number of the faculty are in the Department of Human Oncology and they’re working on similar things.”

“We are very anxious to pursue this work and, as we proceed through drug design, see if we can turn these peptides into therapeutics that in fact help someone who has breast cancer, prostate cancer, many different types of cancer.”

It’s rather remarkable, decoding the intricate and nearly invisible processes that govern our lives. But it’s something that Rapraeger’s team learned through meticulous, step-by-step discovery, through solving puzzles one piece at a time.