that conventional bulk tissue
sampling does not typically
guarantee.
By using chemical labelling
to boost overall sensitivity,
the researchers identified
more than 10,000 proteins
and 17,000 phosphorylation
sites from a 25 microgram
sample. This is comparable with
analysis of larger amounts of
tissue, with the exception of
the phosphorylated-protein
coverage, which was almost
half that typically provided by
a conventional bulk sample.
However, in an analysis of
breast tumours in patient-
derived xenografts — a model
of cancer in which tissue from
a person’s tumour is implanted
in a mouse — the researchers
found that their smaller samples
still showed trends that were
comparable with those derived
from bulk samples, suggesting
that the technique could detect
biological signalling.
As a proof-of-principle, the
researchers used the technology
to profile the genome and
proteome of tumours from
people with ERBB2-positive
breast cancer who were treated
with chemotherapy and anti-
ERBB2 antibodies. In people who
responded to the treatment,
the team detected a statistically
significant reduction in ERBB2
protein phosphorylation in
biopsies collected before and
48–72 hours after treatment.
The trial suggests that this
approach to tumour analysis
could be used to quickly assess
individuals’ responses to
treatment. The authors caution,
however, that the technique
must prove its diagnostic value
in larger studies, which are now
under-way, before it can be used
in the clinic.Nature Commun. 11 , 532 (2020)drug rated top by the VMTB to
47% of people and one of the
first four recommendations
to 75% of people. The majority
of those who did not receive
a treatment recommended
by the system were given
chemotherapy.
The VMTB platform also
increased clinical-trial
enrolment — historically, only
around 5% of people with
pancreatic cancer enrol in trials,
but the average for people
who started a therapy after
a VMTB report was 22%. This
might be due, in part, to the
system’s ability to consider the
distance between a person’s
home and the facilities hosting
clinical trials — something that
would be time consuming for
overburdened clinicians.JAMIA Open 2 , 505–515 (2019)Protein insight from
tiny samples
A new technique for processing
tumour samples significantly
reduces the amount of tissue
required to profile a tumour at
both a genetic and proteomic
level.
Conventional methods
of analysis require about
100 milligrams of tumour
tissue, which is difficult to
obtain without surgery. A
specimen-processing technique
developed by Shankha Satpathy
at the Broad Institute of MIT
and Harvard in Cambridge,
Massachusetts, and his
colleagues, however, requires
less than 20 milligrams of
tissue — an amount that can be
collected in a single needle-core
biopsy.
The tissue-sparing protocol,
known as BioText, splits the
small tissue sample into
numerous layers. These layers
are then shuffled, to ensure
that the portions of tissue
used for DNA, RNA, protein
and histopathological analysis
each contain cells from all parts
of the tumour — somethingwith targets ranked highest
using an algorithm — such as
mutations in BRAF or NTRK —
had a median progression-free
survival of 204 days, compared
with 114 days for all other
volunteers. Oncology specialists
say this study shows the
potential for precision medicine
to extend survival in children.J. Clin. Oncol. 37 , 10011–10011
(2019); J. Clin. Oncol. http://doi.
org/d7dc (2020).Machine learning aids
treatment decisions
A four-year trial at Georgetown
University Medical Centre in
Washington DC suggests that a
cloud-based machine-learning
system can help clinicians to
devise treatment plans for
people with cancer.
Subha Madhavan and her
colleagues developed the
virtual molecular tumour
board (VMTB), which uses
patient-derived molecular
data, real-world evidence from
electronic health records and
databases of biomarkers to rank
treatments for individuals. In all,
the system takes into account
more than 50,000 variables —
many more than any physician
could consider. It then offers
recommendations, and a
clinician makes the final
decision. Compared with
commercial lab reports, the
VMTB was better at identifying
biomarkers useful for therapy or
suitable clinical trials for people
in about 80% of cases.
Between 2014 and 2017, the
platform generated a treatment
plan for 1,725 people, most of
whom had pancreatic cancer
and had already exhausted
multiple lines of therapy. The
volume of cases reviewed each
year grew from 46 in 2014 to 622
in 2017, and the turnaround time
for case review fell from 14 days
to 4 days.
In a real-world analysis of
343 people, clinicians were
found to have prescribed thePrecision shows
paediatric promise
Two studies reported a year
apart have shown that molecular
profiling of childhood cancers
can generate targeted treatment
recommendations.
Children with recurrent
tumours or cancers that are
resistant to treatment typically
have very few options. However,
the two studies demonstrate
that precision-oncology
techniques, which identify
specific genetic changes in the
tumour that can be targeted
with drugs, can extend survival
in some children.
The first study, led by
paediatric haematologist–
oncologist Will Parsons at
Baylor College of Medicine
in Houston, Texas, assessed
how often people under the
age of 21 could be matched to
targeted therapies on the basis
of a molecular alteration. The
researchers estimated that
tumour sequencing would
identify a genetic alteration
that could be targeted with
an investigational therapy in
around 10% of people. However,
their preliminary analysis of
422 people matched 24% of
children with a treatment. The
researchers are now monitoring
a cohort of people to see if the
investigational therapies they
were matched with are effective.
These findings were
bolstered in June, when a large
non-interventional study
led by Cornelis Martinus van
Tilburg at the Hopp Children’s
Cancer Center in Heidelberg,
Germany, reported that a similar
proportion of children (28%)
were candidates to receive
targeted therapies. For a cohort
of 525, the researchers used an
algorithm to identify molecular
targets for off-label treatments
and potential biomarkers for
clinical trials in 149 children.
They also evaluated the clinical
outcome of interventions based
on this information. Although
overall survival was the same
for all participants, the childrenNature | Vol 585 | 24 September 2020 | S3For the latest
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2020
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