"Pretty good"? Pretty good? If that's correct, and from what I've been observing it isn't beyond what's possible (IMO), it's great.
On another note, a webfriend (thanks John) sent me this. This is EXACTLY what Agouron is doing with AG3340, the MMP inhibitor......
Wednesday April 9 6:35 PM EDT
UCSF team to receive $4 million to explore ways to fight cancer by
targeting tumor enzymes
SAN FRANCISCO--(BUSINESS WIRE)--April 9, 1997--The U.S. National Institutes
of Health is awarding $4 million to fund cancer studies by researchers at
the University of California San Francisco who are targeting tumor-made
enzymes.
These enzymes, called proteases, already have been successfully targeted
with protease-inhibitor drugs to combat the AIDS virus, HIV.
The award marks the largest grant funded by NIH's National Cancer Institute
to study the role of proteases in cancer.
Beginning this month, the grant provides steady support for 12 physicians
and doctoral scientists at UCSF to embark on a five-year search-and-destroy
mission aimed at identifying and crippling proteases that are conspicuously
active in tumors.
Proteases are work-performing enzymes that cleave other proteins.
Individual members of the protease family recognize and cleave different
proteins.
A small, but significant and growing body of research suggests that some
proteases are frequently overactive in cancer compared to normal tissue,
according to Marc Shuman, MD, a senior research scientist with the Cancer
Research Institute who will lead the new cancer studies.
Studies by Shuman and his UCSF colleagues show that inhibiting protease
activity can inhibit tumor growth and also migration of tumor cells to
other sites, an ominous event known as metastasis. By identifying and
targeting proteases that may be unusually active in tumors, the UCSF
researchers hope to interfere with protease-regulated signals and
activities that persuade cells to become cancerous, multiply and
metastasize.
"Protease inhibitors may within the next several years become available as
a powerful accompaniment to now-standard cancer therapies," Shuman says.
"Even if protease inhibitors do not destroy cancers outright, they may have
the ability to prevent tumors from growing, spreading and subverting the
functions of normal tissues. With protease inhibitors and other new
therapies that take advantage of the distinctive characteristics of tumor
cells, cancer may become a manageable disease," he adds.
With new drugs, clinicians who treat cancer would be able to combine
compatible treatments, Shuman says. For example, physicians could augment
standard chemotherapy with protease inhibitors, using treatment protocols
similar to those now being used to maintain and improve the health of
persons infected with HIV.
Such a combination of therapeutic punches directed at a tumor may prove
more difficult for a cancer to evade than a narrowly focused strike with
just one type of treatment, Shuman suggests.
To exploit the protease requirements of tumors, Shuman has teamed up with
UCSF colleagues possessing a range of specialties. They include not only
experienced cancer researchers, but also several international experts on
proteases, as well as scientists who specialize in designing drug
prototypes -- molecules that will interact with and disable target
molecules that play a role in disease. The UCSF drug designers have
developed powerful computer software to represent in atomic detail the
molecular structures of target molecules and of these targets' preferred
partners for biochemical interaction.
"Within the scope of this new grant we expect to identify new protease
targets in cancer," Shuman says. "Based on the structures of the targets we
identify, we also believe we will be able to design molecules that can
serve as prototypes for protease inhibitors that will be new and effective
anti-cancer drugs.
"Within this five-year time frame, we anticipate that we will engage in
additional collaborative research projects involving biotechnology
companies, which could lead to clinical drug trials to evaluate new
protease inhibitors," Shuman adds.
The idea of targeting differences between cancerous and normal cells is not
new, but nearly all standard cancer treatments rely on the same basic
approach. Standard chemotherapy drugs and radiation therapy exploit the
contrast between the rapid cell division that occurs in tumors and the lack
of growth that characterizes most normal adult tissues. Current treatments
damage newly forming DNA molecules, genetic material needed by all new
tumor cells.
However, some normal adult cells -- the progenitors of blood cells and of
cells of the immune system, and hair, for instance -- also continue to
divide to make new cells. Standard cancer treatments can damage these
normal cell populations along with tumor cells. In addition, treatment
dosage must be tempered to limit toxicity, and tumors can learn to resist
treatment. Resistance within a population of tumor cells may arise through
genetic mutations that render treatments harmless or that cause drugs to be
expelled from cells.
More recently identified distinctions between cancers and normal tissue --
including differences in protease activity -- raise the prospects for new
cancer treatment strategies that may overcome these drawbacks, Shuman
suggests.
Research studies have shown an association between abnormal protease
activity and human breast cancer mortality, Shuman says, and investigations
of cancer in rodents and of human cancer cells growing in laboratory
cultures indicate that levels of some proteases are frequently elevated, he
adds.
In normal cells and organs, proteases play a multitude of roles, including
the regulation of hormonal signals that guide cellular activities and
growth. Proteases sculpt the molecules that are the forerunners of hormones
into their final, active forms, for example.
Proteases also govern the composition and texture of the membranes that
surround cells in all tissues. These physical qualities of membranes, like
the texture of Braille writing, are themselves a source of information, and
changing membrane composition is another way to influence the
communications between a cell and its surroundings.
The membranes, called "extracellular matrix," also provide physical
containment for cells within an organ or tissue. During normal development
of an organism, proteases break down and reconfigure these extracellular
membranes to accommodate growing body parts.
In an inappropriate and chaotic manner, cancer cells also use proteases to
manipulate the growth-guiding information contained in extracellular matrix
and to break down the membranes prior to spreading beyond their sites of
origin, Shuman says.
CONTACT: University of California, San Francisco
Jeffrey Norris, 415/476-2557 |
