cancer ceases to be a clinical condition that needs only an appropriate
treatment strategy, but continues to be a malady that challenges almost
all of the assumed physiological and medical concepts
It is important to understand in today's era how the marriage of biological
information technology with wet lab screening, diagnostic technologies and
clinical outcome is moving towards bulldozing the stealth walls of protection that
cancer builds around itself. Cancer treatment and management has become more
of a science and art, wherein it has become imperative to tackle aggressiveness,
relapse and resistance with minimal damage ti the quality of life of the affected .
The conscious burden also lies on the need for counseling of the close family
members of the affected to help them understand the risk for future generations
it any a topic where Angelina jolie gets widely discussed
Product-of-Choice in Cancer Management
Precision medicine has become the product-of-choice
cancer management with immunotherapy and targeted
therapeutics adding great clinical benefit to many cancer types.
The fundamental of precision medicine resides on the uniqueness of
the genome of every cancer patient and the tumor microenvironment,
which largely influences cancer aggressiveness. The study of human genome
with increasing awareness of metabolites as well as technologies and
software has taken precision medicine to a level, wherein today Tumor
Mutation Burden (TMB) has also become a quantifiable possibility to
assess prognosis and treatment outcome.
The great boom of artificial intelligence, big data analysis and feasibility
to study the entire human genome would not have been possible if not
for the catalyst technology of Next-Generation Sequencing (NGS).
No genomics report or speculation becomes complete before being
grateful for the technology where everything began Sanger's and
today, the NGS!
The success of the Human Genome project (HGP) albei time
consuming and slow would not have been possible if not for the
technology of sanger's and today the basic science of sequecing
has been explored under multiple explorative chemistries from
semiconductor to amplification and hybridization based to ensurn
massive parallel sequencing has became a reality giving birth to NGS.
The technoligy of NGS emprowered genomics like none other, enabling
the study of ensure the cost per megabase reduces to a great extent ,
making this a clinically favorable platform for use even with the $1000
genome
NGS to Diagnose
Diagnosis, staging and treatment of cancer have journeyed through
different milestones and today all three have found big data analysis
and artificial intelligence to circumvent their individual roadblocks.
NGS as a technology has ensured a wealth of data is made available
for oncologists on every molecular aspect of a cancer patient, right
from low frequency allelic variations, to structural variations including
expression levels. This abundance of data when coupled with an
appropriate bioinformatics analysis ensures the factors around
occurrence, progression, relapse, treatment efficacy and outcome
becomes prophesied. Next-Generation Sequencing as a platform is versatile, as the
massive parallel sequencing ability can be tailared for information
on hot spots or broad gene panels depending on the clinical
requirement which varies for each patient.
The assay to be used in NGS also depends on the stage at
which an oncogenomic test is recommended for the patient.
The reason for NGS-based oncology test will be different for
a repeated treatment failure patient vs. patient newly diagnosed
and looking for a best fit course from the beginning. Every Next-Generation Sequencing
data can be used to derive a disease-oriented highlight
depending on the assay; a popular example to cite here for
better understanding would be individuals looking for a
hereditary cancer test to assess risk and another individual
affected by a hereditary cancer syndrome.
NGS as a platform in the clinical space is widely put to use
for prenatal screening as well as to detect inheritance of
single gene disorders, its utilization in cancer treatment and
management has grown in scope wherein molecular classification
of tumor based on genomic, epigenetic, transcriptomics and
proteomic signatures is being done beyond the conventional
histopathological classification for treatment.
Biomarker discovery by NGS has rapidly changed the face of
histological classification of cancer; an example being brain
cancer. Traditionally brain cancer classification rested on
determining its cell of origin, either astrocytomas or
oligodendrogliomas. However, the 2016 revised guidelines
by WHO on brain tumor strongly recommends integrating
molecular characteristics to diagnose. Clinical biomarkers
bear diagnostic (presence or absence of cancer), prognostic
(determine nature of cancer - aggressive or otherwise),
predictive (determine patient's response to therapy) as
well as pharmacodynamic potential.
The power of Next-Generation Sequencing in oncology can also be attested from
the fact that genetic material from both tissue and blood
can be assayed and this improved the utilization of the
concept of liquid biopsy to a great extent. Liquid-biopsy
based cancer diagnosis works on the principle of studying
tumor cell derived DNA; termed cDNA (circulatingtumor DNA)
Which are present in extremely low concentrations and NGS
has ensured these nanogram quantities of tumor genomic
material become accessible for analysis. Apart from DNA
analysis for studying known and unknown genes, NGS also
facilitates study of exosomes which facilitate intercellular
communication and hence, implicates in cancer metastasis,
angiogenesis, as well as immune invasion. Studying the
profile of RNA molecules within exosomes provides a snap
shot of the liver tumor cell population.
NGS in Precision Medicine
Precision medicine or personalized medicine focuses on the
fundamentals involved in increasing treatment precision by
rigorous patient classification made possible by NGS and
artificial intelligence. Personalized medicine relies on the fact
that each individual is unique and hence, information from a
patient's genes, proteins and tumor microenvironment should
be considered before treatment for better precision.
Targeted therapeutics and immunotherapy has today emerged
to be the treatment of choice and both require a broad range
of molecular information to base outcome. To help this therapeutic
domain grow, Next-Generation Sequencing has played a key role in determining two crucial
tumor-related factors; TMB and Microsatellite Instability (MSI).
TMB as a tissue-agnostic marker indicates response towards anti
PD-L1 or a combination of anti-PD-L1/CTLA4 therapy among
patients with high TMB.
Conclusion
With precision medicine projected to benefit millions of people
in the next 5 years, it is estimated that around 5.1 million
precision cancer diagnostic tests would be performed between
2022-2028 accumulating a market value of nearly $40 million
by 2028.
NGS thus, not only identifies potential actionable mutation
signatures but also influences treatment decisions and
clinical care. To cite one study wherein 42.6% of the
patients received treatment based on NGS outcome,
64.7% expressed overall response rate with the matched
targeted therapeutics. While opinion to have NGS-based
testing for all metastatic tumors as a need is popular, the
concern continues to revolve around cost, counseling and
coverage.
Whatever may be the debate and contraindications for
use of NGS in clinical oncology space, it continues to
grow and remain in the scope of interest for researchers
as well as molecular oncologists who can relate with the
indispensable contribution made by Next-Generation Sequencing in improving
cancer treatment and management manifold.
