NEW YORK, Jan. 16, 2020 /PRNewswire-PRWeb/ -- Many
liver cancer tumors contain a highly diverse set of cells, a
phenomenon known as intra-tumor heterogeneity that can
significantly affect the rate at which the cancer grows,
Mount Sinai researchers report.
The immune system's contribution to this heterogeneity can have
major clinical implications.
In a study published in January in Nature Communications, the
team reported that this heterogeneity—either within the same tumor
or between different tumor regions in the same tumor nodule—appears
in about 30 percent of patients with hepatocellular cancer (HCC),
the most common form of liver cancer, and that some of these tumors
grow rapidly by hijacking different gene networks.
"Tumors are a complex ecosystem, and we're developing for the
first time a blueprint of the different ways they can evolve in
patients with liver cancer by interacting with the immune system,"
says Augusto Villanueva, MD, PhD,
Assistant Professor in the Liver Cancer Program at The Tisch Cancer
Institute at Mount Sinai, and
corresponding author of the study. "By better understanding how
tumors progress, we're learning more about how they adapt to
pharmacological pressures, and how they can develop mechanisms of
resistance to cancer therapies. This greater awareness will
hopefully lead to the identification of biomarkers that can predict
which patients will be responsive to treatment."
Among the clinical implications associated with intra-tumor
heterogeneity identified by the research team was the discovery
that a single liver cancer biopsy could potentially mischaracterize
a liver tumor.
"Some tumors are very homogeneous in terms of their genetic
makeup and immune cell infiltration, while others are very
heterogeneous," says Dr. Villanueva. "This means that a biopsy from
the same tumor could yield different information depending on where
it was taken, and could thus affect clinical decision-making for
the patient. That's why our work aimed at learning how tumors
evolve and the different trajectories they can take is so important
to future cancer research, as well as to effectively treating the
disease."
As immunotherapy continues to transform cancer research and
treatment, one of the most promising areas is liver cancer, which
has become the fastest-rising malignancy in the United States in terms of incidence and
mortality, responsible for 33,000 new cases annually. Two phase 2
clinical trials using PD-1 immune checkpoint inhibitors, which help
the body's immune system recognize and attack cancerous cells, have
achieved unprecedented responses in humans, prompting the Food and
Drug Administration to grant them accelerated approval status for
second-line treatment of advanced hepatocellular cancer.
More recently, a phase 3 clinical trial combining a PD-1 immune
checkpoint inhibitor with an antiangiogenic improved survival
compared to the current first-line standard of care, sorafenib.
Still, only about 30 percent of patients with HCC are believed to
respond favorably to immune checkpoint inhibition—an outcome not
uncommon with immunotherapies.
"The immune system imposes significant constraints on liver
cancer evolution, and by investigating the interaction of immune
cells and cancer cells at the molecular level we're trying to
predict or anticipate mechanisms of tumor resistance," explains
Bojan Losic, PhD, Associate
Professor of Genetics and Genomic Sciences, Cancer Immunology
Program, at Icahn School of Medicine at Mount Sinai, and lead author of the study.
"Our work is particularly relevant considering the remarkable
success of immune checkpoint inhibitors in some heterogeneous solid
tumors."
To understand the mechanisms that drive tumor progression on a
patient-by-patient basis, the research team from Mount Sinai and other medical centers around
the world performed an integrated molecular analysis of gene
expression, immune activities, and DNA mutations from multiple
regions of the same tumor nodule in 14 liver cancer patients. The
study was the first to use single-cell RNA sequencing in multiple
regions of the same tumor nodule, and was among the first to assess
the contribution of the immune system to liver cancer
evolution.
The Mount Sinai-led study
consisted of researchers from the University of Sao Paulo School of
Medicine in Brazil; the University
Medical Center Hamburg-Eppendorf in Hamburg, Germany; Lausanne University Hospital
CHUV in Switzerland; Universitat
de Barcelona in Spain; Clinica Universidad de Navarra in
Spain; Dalhousie University in Halifax, Nova Scotia; and IBM Research.
About the Mount Sinai Health System
The Mount Sinai Health System is New York
City's largest integrated delivery system, encompassing
eight hospitals, a leading medical school, and a vast network of
ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest
care, the highest quality, the highest satisfaction, the best
access and the best value of any health system in the nation. The
Health System includes approximately 7,480 primary and specialty
care physicians; 11 joint-venture ambulatory surgery centers; more
than 410 ambulatory practices throughout the five boroughs of
New York City, Westchester, Long
Island, and Florida; and 31
affiliated community health centers. The Icahn School of Medicine
is one of three medical schools that have earned distinction by
multiple indicators: ranked in the top 20 by U.S. News & World
Report's "Best Medical Schools", aligned with a U.S. News &
World Report's "Honor Roll" Hospital, No. 12 in the nation for
National Institutes of Health funding, and among the top 10 most
innovative research institutions as ranked by the journal Nature in
its Nature Innovation Index. This reflects a special level of
excellence in education, clinical practice, and research. The Mount
Sinai Hospital is ranked No. 14 on U.S. News & World Report's
"Honor Roll" of top U.S. hospitals; it is one of the nation's top
20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology,
Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology,
Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best
Hospitals" issue. Mount Sinai's
Kravis Children's Hospital also is ranked nationally in five out of
ten pediatric specialties by U.S. News & World Report. The New
York Eye and Ear Infirmary of Mount
Sinai is ranked 12th nationally for Ophthalmology, Mount
Sinai St. Luke's and Mount Sinai West are ranked 23rd nationally
for Nephrology and 25th for Diabetes/Endocrinology, and Mount Sinai
South Nassau is ranked 35th nationally for Urology. Mount Sinai
Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount
Sinai South Nassau are ranked regionally.
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SOURCE Mount Sinai Health System