A TAD INTROSPECTIVE--2006

Scientists discover 'scout' system that spreads cancer
NEWSDAY

Why cancers possess a wanderlust, spreading from one site to another, has been one of the most confounding questions in medicine, and now scientists have unmasked the role of infinitesimal "scouts," cells and proteins that coalesce to seek out fertile ground for a tumor's spread.

The finding turns a corner in the history of cancer research, experts say, demonstrating that a series of ominous events lead these scouts - dispatched by the tumor itself - to find fresh ground and lay a foundation for a new cancer. In some cases, the foundation can be laid years before seeds of the new tumor arrive.

"For many years, it was thought that cancer was happening in one way: A tumor developed, a piece of it broke off and traveled through the bloodstream and planted somewhere else. Even though people forever and a day thought that this was the case, we now realize that there is more to it than that," said Dr. Rosandra Reich Kaplan, a pediatric oncologist who holds appointments with Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center in Manhattan.

She said the finding opens a new window on understanding cancer and could soon lead to new diagnostic targets and more treatments.

"We're hoping to conduct a very large trial with patients in about a year or two," Kaplan said.

Dr. Goarav Gupta, a cancer researcher at Memorial Sloan-Kettering who was not involved in the research, broached a similar possibility earlier this year when he described how his studies eavesdropped on the "crosstalk" between the initial tumor and the spot to which it spread. Kaplan and her colleagues delineated the multiple steps.

"This is the first time that anyone has described the events that occur before you get metastasis," said Dr. David Lyden, co-director of the Children's Blood Foundation Laboratory at New York-Presbyterian Hospital/Weill Cornell Medical Center in Manhattan.

"Metastasis is the area of medicine in which we have not been very successful," said Lyden, who with Kaplan and Dr. Shahin Rafii, a professor of genetic medicine at Weill Cornell Medical College, published a report on their studies in a recent issue of the journal Nature. "Once the cancer metastasizes, there is not much that we can do."

Lyden emphasized that it is rarely the initial tumor that proves deadly, but rather its lethal offshoots - the metastatic disease.

In addition, snippets of the tumor itself don't break away to spur new cancers elsewhere; instead, tiny protein growth factors from the tumor stimulate and coalesce with bone marrow stem cells. These aggregates mobilize in the bloodstream to seek fertile ground. Once at the new site, the clusters prepare the tissue for a new cancer. Because the clusters can be identified in the blood, it is possible to interfere with their activity, Lyden said.

Kaplan said tumors seek fertile ground in specific sites. Breast cancers usually spread first to adjacent lymph nodes before going elsewhere. Gastrointestinal cancers spread first to the liver. It is therefore possible to detect clusters en route to their sites as well as those that already have laid a foundation, but have yet to receive a new tumor.--------

Keeper