Pubdate: Wed, 19 Sep 2012
Source: San Francisco Chronicle (CA)
Copyright: 2012 Hearst Communications Inc.
Contact: http://www.sfgate.com/chronicle/submissions/#1
Website: http://www.sfgate.com/chronicle/
Details: http://www.mapinc.org/media/388
Author: Victoria Colliver

POT ELEMENT SEEN AS CANCER BLOCKER

Compound Helps Reduce Spread of Harmful Cells, Researchers Say

Marijuana, already shown to reduce pain and nausea in cancer 
patients, may be promising as a cancer-fighting agent against some of 
the most aggressive forms of the disease.

A growing body of early research shows a compound found in marijuana 
- - one that does not produce the plant's psychotropic high - seems to 
have the ability to "turn off" the activity of a gene responsible for 
metastasis in breast and other types of cancers.

Two scientists at San Francisco's California Pacific Medical Center 
Research Institute first released data five years ago that showed how 
this compound - called cannabidiol - reduced the aggressiveness of 
human breast cancer cells in the lab.

Last year, they published a small study that showed it had a similar 
effect on mice. Now, the researchers are on the cusp of releasing 
data, also on animals, that expands upon these results, and hope to 
move forward as soon as possible with human clinical trials.

"The preclinical trial data is very strong, and there's no toxicity. 
There's really a lot of research to move ahead with and to get people 
excited," said Sean McAllister, who along with scientist Pierre 
Desprez, has been studying the active molecules in marijuana - called 
cannabinoids - as potent inhibitors of metastatic disease for the past decade.

Like many scientific endeavors, connections made between disparate 
elements - in this case, a plant considered a controlled substance 
and abnormal cells dividing out of control - involved a high degree 
of serendipity. The two researchers were seemingly focused on 
unrelated areas, but found their discoveries pointing in the same direction.

Desprez, who moved to the Bay Area from France for postdoctoral 
research in the 1990s, was looking at human mammary gland cells and, 
in particular, the role of a protein called ID-1.

The ID-1 protein is important in embryonic development, after which 
it essentially turns off and stays off. But when Desprez manipulated 
cells in the lab to artificially maintain a high level of ID-1 to see 
if he could stop the secretion of milk, he discovered that these 
cells began to look and act like cancer cells.

"These cells started to behave really crazy," Desprez said. "They 
started to migrate, invade other tissues, to behave like metastatic cells."

Based on that discovery, he took a look at metastatic cancer cells - 
not just standard cancer cells, but those responsible for 
aggressively spreading the disease throughout the body. He found the 
vast majority tended to express high levels of ID-1, leading him to 
conclude that ID-1 must play an important role in causing the disease 
to spread.

Anticancer potential

Meanwhile, McAllister was focused on studying anabolic steroids in 
drug abuse. McAllister, who also made his way to CPMC from Virginia 
in the 1990s, became fascinated with the role nonpsychotropic 
cannabidiol, or CBD, interacts with cancer.

Marijuana's better known cannabinoid - delta-9 tetrahydrocannabinol, 
or THC - had already shown some anticancer properties in tumors, but 
the nonpsychotropic cannabidiol had largely gone unstudied. 
McAllister initial research showed CBD had anticancer potential as well.

About eight years ago McAllister heard his colleague, Desprez, give 
an internal seminar about his work on ID-1, the manipulated protein 
cells that masquerade as cancer cells, and metastases. That produced 
an idea: How effective would cannabidiol be on targeting metastatic 
cancer cells?

The pair teamed up - Desprez with his apparently cancer-causing ID-1 
and McAllister with his cancer-fighting CBD - deciding to concentrate 
their research on metastatic cells of a particularly aggressive form 
of breast cancer called "triple negative." It is so named because 
this type of breast cancer lacks the three hormone receptors that 
some of the most successful therapies target. About 15 percent of 
breast cancers fall into this category, and these cells happen to 
have high levels of ID-1.

Consistent results

When McAllister and Desprez exposed the cells to cannabidiol in a 
petri dish, the cells not only stopped acting "crazy" but they also 
started to revert to a normal state. Both scientists were shocked.

"We thought we did the experiment the wrong way," McAllister said. 
But they got the same results each time they did it.

"I told Sean, ' Maybe your drug is working through my gene,' " Desprez said.

What they found is that the cannabinoid turns off the overexpression 
of ID-1, which makes the cells lose their ability to travel to 
distant tissues. In other words, it keeps the cells more local and 
blocks their ability to metastasize. Cancer kills through its ability 
to metastasize.

The researchers stressed cannabidiol works only on cancer cells that 
have these high levels of ID-1 and these do not include all cancerous 
tumors but, rather, aggressive, metastatic cells. But they've found 
such high levels in leukemia, colorectal, pancreatic, lung, ovarian, 
brain and other cancers.

McAllister and Desprez, who hope to publish results of their research 
before the end of the year, have received various grants through the 
National Institutes of Health, the U.S. Department of Defense, the 
California Breast Cancer Research Program and Susan G. Komen for the Cure.

Pot smoking of no help

Still, no one is suggesting that patients with metastatic cancer 
smoke or ingest marijuana to absorb this potentially cancer-fighting compound.

While cannabidiol, or CBD, is the second-most abundant cannabinoid 
within marijuana, it has largely been bred out of the plant in favor 
of a higher percentage of THC, the active chemical that causes the 
psychotropic high widely associated with the plant.

A long way to go

Martin Lee, director of Project CBD, a Sonoma County group that works 
to raise awareness of the scientific promise of the compound, 
described the cannabidiol research as potent both as a medicine and a 
myth buster.

"It debunks the idea that medicinal marijuana is really about people 
wanting to get stoned," said Lee, author of "Smoke Signals," a book 
published last month about the medical and social history of 
marijuana. "Why do they want it when it doesn't even get them high?"

Lee said the role of marijuana in cancer research is not limited to 
CBD and that further research needs to be done on how it interacts 
with THC for possibly greater effect. "While CBD is quite amazing as 
a molecule, it's really a way of drawing attention to the whole 
plant," he said.

The researchers know there's a long road ahead as they move from 
animal studies into human clinical trials and ultimately turning it 
into a pill or an infused drug that people can take. But they are 
already developing human trial models and hope to test the drug, 
probably in combination with current chemotherapies.

"They've been doing studies on mice and showing the effect in tumors. 
All that is wonderful, but what you don't know is whether it will 
make people go pea green or colorblind," said Dr. William Goodson, a 
breast cancer specialist at California Pacific Medical Center who is 
familiar with the researchers' work.

Patient intrigued

Nonetheless, Goodson said he is intrigued by the potential to inhibit 
the factor that makes triple-negative breast and other cancers 
particularly aggressive. "For people who don't have other options, I 
think that's an exciting possibility," he said.

Patients with triple negative breast cancer are eager, too, about the 
potential of another treatment and hope the research will translate 
into a drug in the pipeline - sooner rather than later.

Susan Rancourt of San Carlos was just diagnosed with triple negative 
breast cancer in July and is in the middle of chemotherapy.

"I don't have doomsday outlook. I feel like I am going to make it 
through this. But the trick is the next five years," said Rancourt, 
59, who is being treated at Stanford. "If this research is advanced 
to the point of something (a drug) in the next five years, that will 
make a difference to me."

Sense of immediacy

As for the fact it is derived from marijuana, Rancourt said that's 
the least of her concerns. "I don't care if it comes from acorns," 
she said. "It's not the source, it's the result."

Desprez also has a timeline. The researcher learned his 41-year-old 
sister was recently diagnosed with aggressive breast cancer that has 
already spread to her lymph nodes. While her cancer is receptive to 
hormone therapies, he's worried about the potential of recurrence of 
metastatic disease - one that lacks the hormone receptors and is even 
more unforgiving.

"I want to be ready for that," he said. "There is a deadline."
- ---
MAP posted-by: Jay Bergstrom