FM AUGUST 2018 ISSUE1 - digital edition

cover story
exosomes from a patient clustered perfectly next to its matched
FFPE tissue sample. The breast cancer specific exosomes looked
almost identical to the matched tissue. The same breadth and
diversity of RNA as seen from the tissue samples has been noted
with more than 12,000 different mRNAs and over 1000 lincRNAs.
Enhancing sensitivity
Similarly, it has been demonstrated that the performance of
mutation testing can be improved by combining exosome RNA
and cell-free DNA, compared to cell-free DNA assays alone.
”You need the exosome compartment to better understand the
biology of the cancer,” comments Dr Johan Skog, chief scientific
officer at Exosome Diagnostics, a Waltham MA-based developer
of biofluid-based molecular diagnostics. “We can also combine
the exosome RNA with the cfDNA to look at the mutations on
both compartments at the same time. This increases sensitivity.”
Exosomes are released as an active process from living cells,
while cfDNA is released from cells dying of apoptosis/necrosis,
he added.
In another recently published study, Exosome Diagnostics reported
the detection of EGFR T790M mutation in plasma from patients
with non-small cell lung cancer (NSCLC).
About 60% of NSCLC patients develop resistance to EGFR
inhibitor therapy due to the EGFR T790M mutation. Patients
who fail therapy due to this mutation will benefit from treatment
with osimertinib. However, performing a repeat lung biopsy to
obtain the mutation status is challenging and cannot be done
on all patients. Detection of EGFR T790M in a liquid biopsy would
solve some of the issues, but it has proven difficult due to low
abundance of T790M positive cell-free DNA in blood.
However, utiliising a proprietary technology , the researchers could
Advantages
• Ease of diagnosis: Liquid biopsies avoid
invasive procedures, repeated biopsies and
overcome the limitation of lacking enough
tissue. It is helpful in inaccessible tumours
• Tumour heterogeneity: It gives more
representative information of the tumour and has
a potential to detect more targetable/actionable
genetic aberrations
• Prognostication: The amount of ctDNA and
the mutational load as well as type of mutations
fosters prognostication at the time of diagnosis
• Prediction of response and effectiveness of
anticancer therapy: The quantity of ctDNA,
mutational load and specific mutations
(appearance of new as well as reversion of old
mutations) can be followed up prospectively
which can help in therapy decisions
• Reassessment: To detect residual disease or
recurrence and or relapse
• Better Monitoring: Screening the
emergence of new alternative genetic
pathways associated with resistance to
current anticancer therapy as well as
reversion of old active pathways which may
warrant change of treatment
Liquid
Biopsy
Challenges
• The tumour associated genetic aberrations can
be lost or gained over the monitoring period
• The tumour associated genetic aberrations can
be lost or gained in response to treatment
• The CTCs may detect aberration limited to
clonal subpopulation
• Identification of tumour DNA requires founder
genetic aberrations (which are not lost during
the progress of cancer) such as APC in colorectal
cancer. These aberrations should not be affected
by the anti-cancer therapy (passive mutations)
• Standardization of the testing methods
• Availability of standardised tests
• Clinical trials of these tests with survival
as endpoints
24 / FUTURE MEDICINE / AUGUST 2018