Even with such potent drugs in the pipeline, another problem must
be overcome before anti-cancer drugs will work well. Some solid
tumors are so large that it is difficult to get any anti-cancer
drug to penetrate deeply inside the tumor. David Ranney says that
chemotherapy works initially to shrink the outside of these tumors.
But the inside never gets the drug and becomes resistant to it by
the start of the next chemotherapy regimen.
At home, patients endure a roller coaster of hope
and despair as their regressing tumors regrow. Ranney estimates
that 95 percent of standard chemotherapy agents are cleared from
the body's bloodstream before ever making contact with a tumor cell.
That's because the body is so good at ridding itself of toxic drugs
via the liver. "No delivery, no payload," says Ranney,
who founded two biotech companies and now runs a Dallas consulting
company called Global Biomedical Solutions.
For enough of a drug to reach the core of a large,
solid tumor, many patients must withstand massive doses of toxic
chemotherapy that kill bone marrow and sometimes heart cells. Raphael
Pollock, chair of the department of surgical oncology and head of
the division of surgery at the MD Anderson Cancer Center, relays
the story of three such unlucky patients. All were cured of tumors
in their muscles and other soft tissues, but the chemotherapy's
side effects required each to undergo a heart transplant.
"Obviously the treatments we have are less than
ideal," says Pollock. But Ranney, attempting to improve drug
targeting and action, has turned to a clever means of encapsulation.
As a pathologist at Northwestern University and elsewhere, Ranney
observed that white blood cells and viruses were two of the biological
agents that could penetrate deep into tissue cells. He also noted
that the cells and germs performed their fait accompli by covering
themselves in sugar. Why not cloak anti-cancer drugs in the same
biological coats that nature has devised?
The concept led Ranney and his colleagues at the University
of Texas Southwestern Medical Center to manufacture a platform of
sugar-based coverings called sulfated glycosaminoglycans. Various
types of sugars are mixed with anti-colon cancer drugs, emulsified
under high pressure, and freeze dried. The powder is later dissolved
and injected into various strains of mice, each with differing solid
tumors. Once inside the animal's bloodstream, the sugars recognize
special molecular receptors on the inner surfaces of blood vessel
walls, similar to locating a house by its address. The sugars then
bind to those sites, pulling the drug with them through the vessel
wall and into the nearby tissue. There, the sugar disguises the
drug from the body's clearance mechanism and eventually leads the
drugs into the depths of the tumor--to their final "street
address," Ranney says. "We are fooling the body into transporting
our own drugs for targeting."
As a bonus, Ranney's team encapsulates the drugs in
a time-release package that releases the chemotherapy payload slowly
and over a longer time, ensuring that a tumor does not shrink slightly
only to regrow soon after remission.
So far, Ranney's work is in its early stages. In one
strain of tested mice, 40 percent experienced complete regression
of their tumors after 90 days with the sugar-coated drug, compared
with 0 percent in control animals given non-experimental forms of
drugs. "With current advances in chemistry," Ranney sums
up, "we are now moving from exposed, highly toxic drugs to
packages of payloads that get the home address of the tumor cell."
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