One of the major advances provided by the use of genomics
in clinical research is the ability to use novel clinical trial
designs to assign the correct therapy to the correct patient
earlier and to improve organ-based classi;cations of cancers
by including a description of the underlying genomic
alterations. Such trials can take the form of basket or
umbrella trials (see Figure 9). Basket trials aim to test one
drug or one particular genetic mutation across multiple
organs. Umbrella trials seek to test a drug or drugs across
multiple genetic mutations within a particular type of
cancer. For example, I-SPY 2 and BATTLE- 2 are umbrella
trials in breast and lung cancer, respectively.
Two ambitious umbrella trials are just getting underway
and are possible only because of advances in DNA
sequencing technology. ;e ;rst of these, the Lung-MAP
In addition, physician-scientists like Nikhil Wagle, MD
(see p. 42), are using genomics to help understand why
some individuals, referred to as rare responders, have
exceptionally good responses to a treatment received as part
of a clinical trial, whereas the majority of individuals do not
gain bene;t from the therapy.
Whole exome sequencing
refers to sequencing only the ~3% of the DNA that codes for proteins,
rather than sequencing all DNA bases.