UCSF Comprehensive Cancer Center Program triumphs with highly coveted grant to conquer prostate canc

By Jennifer O'Brien

UCSF Comprehensive Cancer Center basic scientists and clinical researchers have
received a highly coveted grant from the National Cancer Institute that they
say will fuel their ongoing mission to methodically and aggressively move in on
prostate cancer.

The $11.9 million five-year grant, with an additional $12 million in matching
funds raised by an advocacy group led by Andy Grove, co-founder and chairman of
Intel Corp., is designed to drive a cross pollination of ideas between some of
the world’s leading basic scientists and clinical researchers to improve
prostate cancer treatment, early detection and prevention. First year funding
is $2.3 million.

The so-called SPORE grant, for Specialized Program of Research Excellence, is
unique, as most major basic science grants do not include funding for clinical
research. The grant was awarded to UCSF in recognition of the breadth and depth
of the UCSF Comprehensive Cancer Center’s basic science and clinical research
programs and its ability to integrate these programs for clinical advance.

“Our goal with this SPORE is to take a fresh approach to trying to solve the
significant problems in prostate cancer research,” says Marc A. Shuman, MD,
professor of medicine and director of the new UCSF Prostate SPORE. “We
intentionally sought out outstanding basic scientists who, while not already
studying this disease were interested in changing a significant part of their
effort to work on these problems, and would make a commitment to working
closely with prostate cancer clinicians and clinical scientists.

“Scientists can do great things when they work on a project on their own, but
the most successful strategy for disease-related research is the team approach,
where you integrate successful people representing different specialties,” says
Shuman. And the outcome to such cross pollination is more than additive, he
says. “There’s a synergism.”

The decision to apply for a prostate SPORE grew out of a prostate cancer
program that was committed to a multi-disciplinary effort from the beginning,
says the co-principal investigator of the prostate SPORE, Peter Carroll, MD,
UCSF professor and chair of the department of urology. “The SPORE builds on our
efforts, supporting our commitment to bringing together talented clinicians,
scientists and advocates from various fields who can share their expertise on
one very important problem.”

The NCI has awarded only 23 SPORE grants since the inception of the funding
mechanism in 1992. The grant includes an opportunity for a competitive renewal
after five years. Joe W. Gray, PhD, UCSF professor of laboratory medicine and
radiation oncology, leads a breast cancer SPORE, now in its eighth year of

The UCSF prostate SPORE supports six programs, which include an investigation
of why some prostate cancers resist therapies aimed at reducing the
growth-promoting effects of testosterone on tumors; a study of whether
genetically engineered viruses can be used to combat prostate cancer; a project
to develop novel engineered antibodies to fight cancer; and research on an
antibody that stimulates an immune-system response against prostate cancer. The
programs also include an investigation of which genes contribute to prostate
cancer and a study of genes that confer susceptibility to prostate cancer or to
virulence of tumors in humans.

The SPORE also includes six core resource programs: administrative; tissue;
informatics; advocacy; clinical research and animal technology.

The goal of each research program is to enrich the flow of information between
basic scientists and clinical researchers. Shuman, who treats patients with
prostate cancer, will participate in the lab meetings of Alan Balmain, PhD,
UCSF professor of biochemistry, who is working to identify genes in mice that
confer susceptibility or resistance to cancer, and genes that determine a
cancer’s virulence. The expectation is that Balmain will eventually identify
the equivalent genes in humans, and that Shuman will be able to study the
implications of these genes in a clinic he is establishing for people at high
risk for prostate cancer based on a strong family history.

Jim Allison, PhD, UCSF clinical professor of medicine, professor of molecular
and cell biology, UC Berkeley, and a Howard Hughes Medical Institute
investigator, who has made what Shuman calls “spectacular discoveries” in mice
about how the immune response to cancer is regulated, is now working with
clinical investigator Eric Small, MD, UCSF associate clinical professor of
medicine, whom Shuman calls one of the best oncology clinical researchers in
the world. Allison has developed an antibody that activates the immune response
in mice. The antibody appears to have a major impact on thwarting prostate
cancer in a transgenic animal model. Small has now begun a phase I clinical
trial of the antibody in patients with advanced prostate cancer.

“Basic scientists don’t know much about some of the really important clinical
features of disease, and clinicians don’t have the basic science background to
do the research that the basic scientists can do,” says Carroll. “When you get
these two groups working together, which we really do, you’re able to make the
most progress the most rapidly.”

Prostate cancer affects one in six American men, and will claim an estimated
37,000 lives this year. The cost of treatment is high, and there is a lack of
consensus regarding the best form of treatment for each stage of the disease.
In addition, the causes of prostate cancer are believed to be multiple,
including genetic elements, as well as racial, cultural, and environmental
factors, such as diet.

The success in receiving the SPORE grant, says Shuman, is due in no small part
to the UCSF prostate cancer advocacy group, made up of current and former UCSF
prostate cancer patients or family members, and led by Andy Grove, of Intel
Corp., and Yahoo! board member Arthur Kern. Grove, a prostate cancer survivor,
consulted Carroll during his treatment.

In addition to making personal contributions during the last two years, the
advocacy group has raised nearly $12 million in matching funds for the prostate

“UCSF’s success in receiving the prostate SPORE grant indicates the NIH’s
[National Institutes of Health’s] recognition of the quality and
interdisciplinary nature of the research conducted at UCSF. I’m particularly
excited about the grant because it is my conviction that diseases are most
likely to be cured by collaboration across disciplines, and between scientists
and clinicians, which is what SPORES are meant to encourage,” Grove says.

“UCSF’s success in receiving the prostate SPORE grant indicates a recognition
by the NIH [National Institutes of Health] of the quality and interdisciplinary
nature of the research conducted at UCSF. I’m particularly excited because it
is my conviction that diseases are most likely cured by collaboration across
disciplines, and between scientists and clinicians, which is what SPORES are
meant to encourage,” Grove says.

“The advocates were tremendously helpful in helping us get the grant, because
their financial commitment helped convince the NCI how committed we are,” says
Shuman. “And the business expertise that Art and Andy provide us is fantastic.
They contribute an enormous amount of valuable guidance on executive and
administrative issues.”

Carroll concurs. “Our advocates do more than just raise money—they helped us
to organize our efforts effectively, and to focus on issues that matter most to
patients,” he says. “Most importantly,” he adds, “they give us a real urgency
to attack and solve this problem of prostate cancer.”

Shuman, too, brings a personal angle to the story. A prostate cancer survivor,
he says he has both an academic and personal interest. “I couldn’t be more
excited,” he says. “My goal is to make us the best organ-specific cancer
research program in the world.”