* Genentech, Curis drug GDC-0449 shrank skin cancer tumors
* Brain tumor patient responded, but developed resistance
By Julie Steenhuysen
CHICAGO, Sept 2 An experimental cancer pill
made by Roche's ROG.VX Genentech shrank tumors in patients
whose skin cancer had spread, raising hope for a new class of
drugs that may have an affect on many other cancers as well,
U.S. researchers said on Wednesday.
In an early-stage study, the drug being developed in
partnership with Curis Inc (CRIS.O), shrank tumors in half of a
small group of patients with basal cell skin cancer that had
spread to their organs.
The results were so promising they started phase 2 studies.
They also have trials in colorectal and ovarian cancer.
But there's a possible hitch.
While the compound -- known as GDC-0449 -- also helped
shrink tumors in one patient with an aggressive type of
childhood brain cancer called medulloblastoma, that patient
eventually developed resistance to it.
The studies, published in the New England Journal of
Medicine and the journal Science, offer a first look a
promising new class of drugs that block the Hedgehog signaling
pathway, which involves several proteins that play a role in
It gets its name from fly embryos, which take the shape
of spiny little hedgehogs when a gene in the pathway is
Other companies studying Hedgehog inhibitors include
Bristol-Myers Squibb (BMY.N) and partner Exelixis Inc (EXEL.O),
and Infinity Pharmaceuticals (INFI.O).
Dr. Charles Rudin of the Johns Hopkins Kimmel Cancer
Center, who worked on the studies, said the Hedgehog signaling
pathway appears to play a role in lots of cancers, but it seems
to be particularly important in medulloblastoma and basal cell
carcinoma, the most common type of skin cancer.
"We know that both of these cancer types have mutations in
Hedgehog pathway genes, and our results with Hedgehog
inhibitors could be the starting point for developing a new
type of therapy for these intractable cancers," he said.
In most patients, basal cell skin cancer is easily treated
with surgery. But in a rare few, it spreads.
"There are very, very rare cases where the disease can
metastasize or become so advanced where you can't remove it
anymore. Those are the people who were treated," said Dr.
Josina Reddy, a Genentech researcher who worked on the study,
said in a telephone interview.
The researchers tried the drug in 33 patients, and more
than half responded. Out of 18 patients whose cancer had spread
to their organs, 15 saw their tumors shrink by 30 percent.
Rudin said the response lasted for an average of nine
months, and some patients have continued to benefit for close
nearly two years.
In a 26-year-old patient with brain cancer, the drug shrank
tumors throughout his body within weeks. "It was quite
dramatic," said Rudin, but it was short lived.
Within two months, the tumors came back. Experiments showed
tumors had developed a mutation that blocked the drug's
Dr. Andrzej Dlugosz of the University of Michigan, who
wrote a commentary in the New England Journal of Medicine, said
the studies raise hope for a new class of cancer drugs.
And he said the mutation issue is not a deal breaker.
"It certainly raises concerns regarding how able the cells
are to develop mutations, but hopefully, there will be a way
(Editing by Cynthia Osterman)