Researchers Discover Link Between Organ Transplantation and Increased Cancer Risk
PHILADELPHIA,
July 16, 2008 – Researchers have determined a novel
mechanism through which organ transplantation often leads to
cancer, and their findings suggest that targeted therapies may
reduce or prevent that risk.
In the July 15, 2008, issue of Cancer Research, researchers at Harvard
Medical School found in animal and laboratory experiments that the
anti-rejection, immunosuppressive drug cyclosporine ramps up
expression of vascular endothelial growth factor (VEGF), which
signals the growth of new blood vessels that can feed tumors.
They also found that simultaneously administering an anti-VEGF
therapy with cyclosporine in mice repressed this tumor growth.
Several inhibitors of VEGF are already in use in human cancer
therapy.
The findings could offer some good news for the 15 to 20 percent of
transplant patients who develop cancer within a decade of receiving
new organs, according to the study’s senior investigator,
Soumitro Pal, Ph.D., an assistant professor at Harvard Medical
School’s Transplantation Research Center at Children’s
Hospital in Boston.
“It may be that anti-VEGF agents given judiciously after
transplantation can reduce future cancer occurrence,” he
said.
VEGF expression is markedly increased in patients
post-transplantation, and this can aid in the development of a
blood supply to a transplanted organ, helping it survive and
thrive. “But once the organ has stabilized, it may be
possible to lower the level of VEGF expression to prevent tumor
growth,” he said. “We would need to figure out how to
balance benefit and risk to keep cancer at bay.”
Tumors that develop after transplantation may have three potential
sources: they may have pre-existed or could have been a recurrence
of previous cancer – and in both of these cases, a
patient’s pre-transplant immune system might have kept these
cancers in check – or cancer-causing viruses could have come
from the donor organ. Physicians have long observed that
immunosuppressive agents, such as the class of calcineurin
inhibitors that includes cyclosporine, appear to promote cancer
development, often in organs that are not transplanted, but the
cause of this was unclear. The Harvard team tested the ability of
cyclosporine to promote growth of pre-existing tumors in mice
implanted with human renal (kidney) cancer cells. Mice treated with
the agent formed tumors faster than untreated mice, but anti-VEGF
therapy substantially reduced that excessive growth.
Digging deeper into the biological pathway of VEGF activation, the
scientists found that cyclosporine activates two of the three forms
of the common protein catalyst, protein kinase C, which leads to
increased expression of VEGF.
“We think PKC-mediated VEGF transcriptional activation is a
key component in the progression of cyclosporine-induced
post-transplantation cancer,” Pal said. “It is likely
not the whole story, but this gives us a clue that we might be able
to use existing or novel therapies to reduce cancer risk in
transplanted patients.”
The mission of the American Association for Cancer Research is to
prevent and cure cancer. Founded in 1907, AACR is the world’s
oldest and largest professional organization dedicated to advancing
cancer research. The membership includes more than 28,000 basic,
translational and clinical researchers; health care professionals;
and cancer survivors and advocates in the United States and 80
other countries. AACR marshals the full spectrum of expertise from
the cancer community to accelerate progress in the prevention,
diagnosis and treatment of cancer through high-quality scientific
and educational programs. It funds innovative, meritorious research
grants. The AACR Annual Meeting attracts more than 17,000
participants who share the latest discoveries and developments in
the field. Special conferences throughout the year present novel
data across a wide variety of topics in cancer research, treatment
and patient care. AACR publishes five major peer-reviewed journals:
Cancer Research; Clinical Cancer
Research; Molecular Cancer Therapeutics; Molecular Cancer
Research; and Cancer
Epidemiology, Biomarkers & Prevention. Its most recent
publication and its sixth major journal, Cancer Prevention Research, is
dedicated exclusively to cancer prevention, from preclinical
research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and
their families, patient advocates, physicians and scientists.
CR provides a forum for
sharing essential, evidence-based information and perspectives on
progress in cancer research, survivorship and advocacy.
Media Contact:
Jeremy Moore
267-646-0557
Jeremy.moore@aacr.org
Posted: July 2008
