Kidney Cancer Journal 95
MEDICAL INTELLIGENCE
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ipated in 2018 for the pivotal TIVO-3 trial, a randomized,
controlled, multicenter, open-label study comparing
tivozanib to sorafenib in patients with refractory advanced
RCC.
Natera and Fox Chase Cancer Center
to collaborate on kidney cancer study
SAN CARLOS, CA—Natera, Inc. has partnered with Fox
Chase Cancer Center to assess the company’s Signatera™
(Research-Use Only) customized circulating tumor DNA
(ctDNA) assay for recurrence monitoring of kidney cancer.
The study will analyze biological specimens collected and
banked from 49 patients diagnosed with kidney cancer—
including a group whose cancer recurred and a group that
did not recur after three years or more. The study will use
Natera’s proprietary customized assay and next-generation
sequencing (NGS)-based technology to determine
whether Signatera (RUO) can be used to distinguish between
the recurring and non-recurring kidney cancer
cases. The study will be led by Philip Abbosh, MD, PhD, assistant
professor, Molecular Therapeutics Program, Fox
Chase Cancer Center.
“There is a paucity of data for circulating tumor DNA in
kidney cancer. This research study will explore a novel approach
for disease recurrence and treatment response
monitoring in kidney cancer, since existing methods have
limitations with sensitivity and specificity,” Dr Abbosh said.
“Determining the relationship between kidney cancer genetic
profiles and prognosis including recurrence using the
Signatera assay has great potential to improve patient care
by detecting cancer recurrence earlier, assisting adjuvant
therapy decision-making, determining treatment effects,
and assessing the need for intervention during follow-up.”
Discovery of kidney cancer driver
could lead to new treatment strategy
CHAPEL HILL, North Carolina — University of North Carolina
Lineberger Comprehensive Cancer Center scientists
have uncovered a potential therapeutic target for kidney
cancers that have a common genetic change. Scientists
have known this genetic change can lead to an overabundance
of blood vessels, which help feed nutrients to the tumors.
Their latest finding shows a potential new cancerdriving
pathway.
More than 90% of the most common type of kidney
cancer have a genetic change that leads to the loss of an
important tumor suppressor gene called VHL. In a study
published in the journal Science, researchers identified a
new downstream effect of this genetic change that is helping
to drive kidney cancer: They found that a protein called
ZHX2 over-accumulates in these cells and helps to turn on
other signals involved in cancerous growth. Their findings
suggest that ZHX2 is a potential new therapeutic target for
clear cell RCC.
Targeted therpies block cell signals involved in abnormal
blood vessel production — which is a downstream effect
of VHL loss — that are part of the standard of care.
Patients can show little response to these drugs or can develop
resistance, so Zhang and his colleagues wanted to
search for other targets that accumulate in cells lacking
VHL function that help to drive the abnormal cancerous
growth.The researchers created a screening technique to
discover new molecules that might help drive cancer when
VHL is lost. This led them to determine that kidney cancer
cells lacking VHL usually had more ZHX2. By eliminating
ZHX2 from their laboratory models, they inhibited cancer
cell growth, invasion and the cancer’s spread. In addition,
they saw that it was involved with signals that can help
cancer cells grow. KCJ
population-based prospective cohort study. Cases had entered
the cohort up to 5 years before diagnosis, and controls
were matched on cases for date of birth, date at blood
donation, sex, and country. The incidence rate ratio (IRR)
of RCC for a doubling in KIM-1 concentration was 1.71,
corresponding to an IRR of 63.3, comparing the 80th to
the 20th percentiles of the KIM-1 distribution in this
sample. Compared with a risk model including known risk
factors of RCC (age, sex, country, body mass index, and
tobacco smoking status), a risk model additionally including
KIM-1 substantially improved discrimination between
cases and controls. High plasma KIM-1 concentrations
were also associated with poorer survival.
Conclusion: Plasma KIM-1 concentrations could predict
RCC incidence up to 5 years prior to diagnosis and were
associated with poorer survival. KCJ
Image shows clear cell renal cell carcinoma with ZHX2 highlighted in
brown. Credit: Jing Zhang, PhD