Despite the fact that cancer remains a feared disease, these days it is far from a certain death sentence - if it is caught early. Metastases are another matter; while they, too, can be successfully treated, the odds for patients are certainly worse once a cancer has metastasized.

But at last week's meeting of the American Association for Cancer Research, there was palpable optimism that scientists would find ways to beat metastasis, as well. In the educational session "How Good Are Our Models for Cancer Invasion and Metastasis?" Lynn Matrisian, professor of cancer biology at Vanderbilt University, told a standing-room only audience that "targeting metastases is a very viable way of targeting cancer."

Breast and prostate cancers - two of the most common cancers in women and men, respectively - both metastasize preferentially in bones. Several presentations and posters at the conference addressed bone metastases, ranging from very basic technology advances to approved therapeutics.

In one poster session, scientists from Pennsylvania State University described a bioreactor that allowed them to let cells grow undisturbed for up to 30 days. First author Laurie Shuman explained that "we are taking tissue culture one step further by allowing cells to behave more like they would in vivo," adding that the goal is maximum similarity to the in vivo microenvironment.

Several observations support the scientists' belief that their bioreactor is closer to this microenvironment than traditional cell culture: Cultured cells made dense layers instead of a single layer, and bone-producing cells that were left in the reactor for up to 10 months appeared to produce bone chips.

At the other end of the bench-to-bedside spectrum, Trevor Powles, emeritus professor of breast oncology at Britain's Institute for Cancer Research, presented data showing that bone metastases can be prevented by targeting not tumor cells themselves, but the bone-eating cells known as osteoclasts, and that improved survival in breast cancer patients.

The fact that osteoclasts are part of what makes bones a frequent suite of metastases has been known for more than a quarter of a century, and the FDA issued an approvable letter in January for Schering AG's Bonefos (clodronate) to reduce the occurrence of bone metastases in breast cancer patients post-surgery.

Powles said the approach of targeting bone rather than tumor cells "really opens up a whole idea of where we might be able to go with therapeutics that is different from anything else - instead of always thinking of the tumor, can we think about all the places where [metastases] can develop?"

For those looking for the big picture, at the educational session on models for metastasis and invasion, Danny Welch, of the University of Alabama, gave a combined history lecture and overview of what metastasis actually is, noting that it is an astonishingly inefficient process.

"Millions of cells per gram of tumor enter the bloodstream every day," he said. "So lots of cells begin the process of metastasis, but few complete it."

Furthermore, there is no single activity that metastatic cells do that normal cells do not. In the end, it is abnormal proliferation - Welch suggested that the minimum size requirement to be considered a metastasis should be 50 cells - at a distant site that makes a metastasis. Anything less than that is close but no cigar, or as he put it, "If I flew to London and went to Wimbledon and stood on Center Court, it would not be enough to make me a Wimbledon champion."

Welch noted that his suggestion of 50 cells is based on old literature, where scientists observed that many cells can make it into the bones and divide five to six times, making colonies of 32 to 64 cells fairly common.

"To the graduate students in the room: there is literature before Medline," Welch said, noting that young scientists often become overly reliant on modern information technology, so that what they think of as their revolutionary breakthroughs can, in the worst case, be no more than a replication of experiments that have been done very elegantly decades ago.

"Take the time to go work in the dusty part of the library - there's really good stuff out there," he said.