IN THE PIPELINE:Cancer Drugs Chase 'Hedgehog' In Disease Fight
July 14 2009 - 10:30AM
Dow Jones News
When cancer researchers talk about a promising area of research
called the hedgehog pathway, they aren't studying spiny little
mammals.
Rather, the term references a series of reactions inside a cell
believed to play a key role in the proliferation of certain
cancers. As a result, many companies including Roche Holding AG
(RHHBY), Infinity Pharmaceuticals Inc. (INFI) and Bristol-Myers
Squibb Co. (BMY) are developing drugs - called hedgehog inhibitors
- that block the pathway and aim to limit the spread of cancerous
cells
Any such drugs, though, aren't likely to hit the shelves until
the first half of the next decade.
The hedgehog pathway got its name when researchers studying body
development found it was responsible for creating mutant fly larvae
that were furry, like little hedgehogs.
In humans, the pathway is mostly dormant except during embryonic
development, when it plays a key role in cell differentiation from
determining organ formation to the placement of your fingers. This
role designates the drugs in development as off-limits to pregnant
women.
Specifically, the hedgehog pathway causes problems when it
produces signals that promote tumor survival and growth. This
occurs from mutation or by being switched on by tumors to make the
environment more conductive for disease growth.
Drug companies are working on compounds stop to this process, by
blocking the specific protein that does the signalling in the
cell.
Because such drugs would only prevent tumor growth, they would
be used in conjunction with commonly used chemotherapies. In some
cancers it is believed that using hedgehog inhibitors may allow
such cell-killing therapies to have better access to cancer cells
and make overall treatment more effective.
Roche's Genentech, working with Curis Inc. (CRIS), is leading
the pack with its compound GDC-0449, which is currently in Phase II
studies in basal cell carcinoma, colorectal cancer, and ovarian
cancer.
Infinity Pharmaceuticals is developing IPI-926 in a Phase I
study in solid tumors and expects to move forward with later stage
trials in a number of cancers including pancreatic, small-cell lung
cancer, and some blood cancers.
Bristol-Myers and Exelixis Inc. (EXEL) are also in Phase I
development of BMS-833923 in patients with advanced solid
tumors.
All these therapies generally mimic the action of a natural
compound called cyclopamine, that was discovered in the 1950s as
the cause of a number of sheep being born with one eye, a condition
called cyclopia.
Cyclopamine isn't potent enough to be an effective treatment in
humans, but it is thought to bind to the signalling protein, thus
halting its activity down the pathway.
Because the drugs are in early development, the full extent of
potential side effects isn't known. But the targeted nature of the
treatments and lack of hedgehog activity in adults has researchers
hopeful that adverse effects will be minimal with prolonged
use.
David Tuveson, an oncologist at Cancer Research UK studying
Infinity's compound in pancreatic cancer with no connection to the
company, would be happy to trade side effects for a patient benefit
in the especially lethal form of the disease where survival is
measured in weeks.
"If we are treating pancreatic cancer for more than a year, that
is a problem I can deal with," he said.
-By Thomas Gryta, Dow Jones Newswires; 212-416-2169;
thomas.gryta@dowjones.com