263cancer may be much less relevant to prognosis and response to therapy than the
array of causative mutations (Kandoth et al. 2013 ). As a result, patients diagnosed
with a cancer for which there are few therapeutic options may increasingly benefi t
from drug therapies originally aimed at other cancers that share common driver
mutations. Sequencing enables the advance from current approach of targeted
searches for specifi c mutations in individual cancers to widespread use of approaches
that survey the entire genome.
In the future, research into cancer genomes will expand and cooperative global
initiatives will generate full genome sequences of various cancers, yielding complete
catalogues of somatic mutations in each one. These studies will reveal essentially the
full repertoire of mutated cancer genes, enabling us to determine how many and
what combinations of mutated cancer genes are necessary to generate an individual
cancer. Sequencing will evolve from a research tool to cancer diagnostic. The rapid
development of NGS technologies seems likely to be transformative. Within a few
years, a complete cancer genome sequence will be obtainable for a few hundred dol-
lars. It will important to incorporate analysis of the genome and transcriptome more
widely into clinical trials in order to exploit the full clinical potential of information
within the cancer genome and generating new and unexpected predictors of drug
responsiveness and prognosis to enable personalized management of cancer.
Single gene testing in cancer is no longer adequate, especially with the growing
numbers of targeted therapies, both currently FDA-approved and in the pipeline. If
a lung tumor is not being driven by EGFR, then one immediately wants to know
whether ALK is involved, and if not ALK then what about ROS, MET, PIK3CA,
etc. There is a need for looking at multiple genes rather than a few select biomark-
ers. Therefore, sequencing of tumor at the time of diagnosis can give valuable guid-
ance for choosing the right course of treatment, but many physicians only turn to
large gene panels as a last resort, when the patient’s tumor has not responded to
conventional therapy or becomes metastatic.
Multiplex gene testing in cancer is still something of a controversial topic. One
point of controversy is clinical. Clinicians often do not want too much information
early on because it complicates their treatment planning. There are computational
tools available online that can help interpret this avalanche of molecular information
and give clinicians an easy-to-understand roadmap for each patient’s treatment.
The other controversial issue is responsibility for payment for NGS. Genetic
testing is perceived as expensive, but it is really no more expensive than the CAT
scans and MRIs that are already commonly used serially throughout a course of
treatment. The payers will soon come to understand that comprehensive gene test-
ing saves money by using a patient’s biomarkers to avoid unnecessary courses of
expensive standard therapies that would are ineffective or even toxic to the patient.
Genetic information that a physician needs is not always specifi c to the tumor.
A targeted panel contains genes that have been carefully selected for the role they
play in tumor formation, tumor treatment, or drug metabolism. Inherited G6PD
gene mutation is helpful information, because it is predictive of an adverse reaction
to oxidants, a class of drug that can induce a highly oxidated state. Other genes may
be relevant and it is a good practice for every new cancer patient to have their tumor
genome sequenced at the time of diagnosis.
Role of Sequencing in Personalized Therapy of Cancer