and free DNA into a patient’s blood. Researchers have
shown in clinical trials that it is possible to use a blood
sample, or liquid biopsy, rather than a traditional tissue
biopsy, to obtain material that can be analyzed to provide
information about the genomic alterations in a patient’s
cancer. Liquid biopsies have the potential to transform
patient care across the clinical cancer care continuum.
The revolution in cancer diagnosis and monitoring began
in June 2016, when the FDA approved the first liquid biopsy
companion diagnostic test for identifying whether or not
a patient with metastatic NSCLC is eligible for treatment
with the EGFR-targeted therapeutic erlotinib. The cobas
EGFR Mutation Test v2 was already approved by the FDA
for testing tumor tissue samples obtained by a traditional
biopsy. The new approval allows the test to be used to
analyze plasma, the colorless liquid component of blood.
Triggering Leukemia Cell Death
CLL is the second most common type of leukemia diagnosed
in the United States, with almost 19,000 new cases projected
to be diagnosed in 2016 ( 3). Tremendous progress has been
made against CLL in the past 2 years, with several new
molecularly targeted therapeutics approved by the FDA for
treating patients with the disease, like David Rampe [who
was featured in the AACR Cancer Progress Report 2014 ( 1)].
Although the new therapeutics benefit many patients with
CLL, not all patients have a response to these treatments.
Moreover, many patients whose CLL initially responds
eventually have disease progression. Patients who have
CLL characterized by a genetic mutation called the 17p
deletion are particularly prone to poor outcomes.
In April 2016, the FDA approved the molecularly targeted
therapeutic venetoclax (Venclexta) for treating CLL shown
to have a 17p deletion with the Vysis CLL FISH Probe Kit
companion diagnostic. This approval provided ne w hope
to patients like Brian Parkinson (see p. 76).
CUTTING CANCER’S LIFELINE FIGURE 14
Venetoclax (Venclexta) is a molecularly targeted therapeutic
that works by blocking the protein BCL2, which promotes
cell survival by preventing cells from undergoing a natural
self-destruct process called apoptosis. It is currently the
only anticancer therapeutic of its kind to be approved by
the U.S. Food and Drug Administration (FDA). Many years
of basic, translational, and clinical research underpinned the
development of venetoclax. The term apoptosis was first coined
in 1975. A decade later, researchers discovered BCL2 and then
went on to show that its function was to prevent apoptosis.
The development of the first BCL2-targeted therapeutic to
enter clinical trials, navitoclax, was hampered by the fact that it
causes platelet death, which limits the dose that can be given.
Venetoclax was approved for treating patients with chronic
lymphocytic leukemia (CLL) shown to have a 17p deletion with
the Vysis CLL FISH Probe Kit companion diagnostic in April 2016.
1975 1985 1988 1992 2000 2006 2007 2011 2016
BCL2 shown to
found to be
in CLL cells.
defined as a
hallmark of cancer.
to kill platelets;
a dose-limiting effect.
enters phase I
clinical trials. FDA approves
to treat CLL with
a 17p deletion.
trials for various