THURSDAY, Nov. 3, 2005 (HealthDay News) -- Overactivity of a key enzyme found in skin cancer cells appears to play a prominent role in triggering the aggressive spread of the disease, a new study suggests.
The enzyme -- known as focal adhesion kinase (FAK) -- is present in every cell of the human body, and is critical to the healthy promotion of many cellular activities.
However, this enzyme's unhelpful behavior within malignant melanoma cells is now gaining scientific attention.
The researchers noted that the FAK enzyme has previously been found to be overactive across a wide range of aggressive malignancies, including eye, prostate, thyroid, colorectal, ovarian and oral cancers.
The current work raises the hope that a better understanding of FAK's role may ultimately lead to the development of new early stage treatments that hone in on the enzyme and halt its ability to promote the migration of malignant cells throughout the body.
Such metastasizing of a localized and curable cancer can make melanoma much more difficult to treat and control -- even leading to an otherwise preventable death, the study authors said.
"FAK has been shown for a lot of different types of cancers to play a role in the tumor cells' ability to move within the body and set up shop, so I think targeting it to reduce the risk of melanoma metastasizing is a very exciting idea," said study author Angela R. Hess, a research scientist at Children's Memorial Research Center in the Feinberg School of Medicine at Northwestern University. "But this is in its very early infancy as a therapy."
The American Cancer Society notes that the incidence of melanoma in the United States has tripled over the past 50 years -- nearly doubling in the last decade alone. Its estimates indicate that nearly 60,000 new cases of melanoma will be diagnosed in 2005, resulting in about 7,770 deaths.
Hess and her team conducted lab analyses on samples of both aggressive and non-aggressive human skin and eye cancer cells.
In the November issue of Cancer Research, the authors report that cancer cell aggressiveness appeared to be a function not so much of elevated FAK levels, but rather of elevated FAK activity.
"The important thing is that the cancer cell, in and of itself, has a very deregulated system so the FAK protein can make the cell go wild when it's inappropriately active," Hess noted.
Such increased enzyme activity was associated with an overall increase in the melanoma cancer cell's ability to move beyond the borders of the tumor and invade healthy areas of the body, the researchers said.
In addition, increased FAK expression was associated with an increase in so-called tumor cell plasticity, in which a cancerous cell improves its chances of spreading by forming its own vascular network to masquerade as an otherwise healthy cell.
The researchers further found that when they blocked FAK activity in certain aggressive cancer cells, the diseased cells displayed a 70 percent drop in their ability to migrate, and a 60 percent drop in their ability to invade tissue outside the tumor area. Tumor cell plasticity was also observed to be halted when FAK activity was neutralized.
The authors concluded that FAK appears to play a kind of gatekeeper role in the opening up of pathways that promote the spread of cancer cells throughout the body. And while they acknowledged that the signaling mechanism that FAK activity initiates is not yet fully understood, they noted that a selective disruption of FAK behavior might slow cancer down.
"Basically the major point is that we're trying to understand what enables melanoma tumor cells to move out from the initial primary tumor to another site in the body, because once that happens melanoma tends to become very difficult to treat and the five-year survival rate drops considerably," Hess said.
"So this is just an idea," she stressed. "And it takes a while to actually produce a drug. But potentially, at some point in the future, we can somehow focus on that specific FAK protein to stop the melanoma from moving."
A similarly cautious tone was sounded by Dr. Jean-Claude Bystryn, a professor of dermatology at New York University School of Medicine, and former head of the melanoma program and vaccine clinic at New York University Medical Center in New York City.
"Trying to find ways to slow the progression or spread of cancer is clearly a very major challenge," said Bystryn. "But at this stage, it's difficult to tell what the best approach is going to be because there are multiple mechanisms that are involved in the spread of cancer."
"So these molecules of FAK may be involved," he added, "and there's always hope that interfering with one of these mechanisms will be effective in slowing the spread. So from my perspective, it's worthwhile exploring --assuming that you know that we're not really sure if this is going to work or not."
More information
For more on melanoma, check with the American Cancer Society.
