cancer. Umbrella trials test multiple therapeutics across
multiple genetic mutations on a group of patients, all of
whom have cancer arising in the same anatomic site.
As our knowledge of cancer biology grows at an ever-quickening pace, continued and increased dialogue among
researchers, regulators, and the pharmaceutical industry
is essential to provide the right patients access to the best
anticancer therapeutics that have been proven to be safe
and highly effective in well-designed, well-conducted
clinical trials at the earliest possible time ( 105).
Dialogue among researchers, regulators, and the
pharmaceutical industry is also important as physician-scientists look to use genomics to identify patients who
might benefit from therapeutics not previously FDA
approved for their type of cancer, an approach known as
drug repositioning or drug repurposing.
One patient who is benefiting from drug repositioning is
Luke Theodosiades, who was just 11 years old when he
was diagnosed with acute lymphoblastic leukemia (ALL)
(see p. 58). After his leukemia did not respond well at all to
intensive standard-of-care chemotherapy, Luke’s team of
physicians at Children’s Hospital of Philadelphia were very
concerned and pursued a specialized genomic analysis of his
leukemia cells performed by researchers at the University of
New Mexico. This analysis found that his leukemia cells had
undergone genetic recombination (see sidebar on Genetic
Mutations, p. 20), resulting in the fusion of two genes
(GOLGA5 and JAK2). The GOLGA5-JAK2 fusion gene
generated a new protein that was driving the multiplication
of Luke’s leukemia cells and likely conferred resistance to
his initial chemotherapy. Because JAK2 is a protein targeted
by ruxolitinib (Jakafi), which was first approved by the
FDA in 2011 for treating adults with myelofibrosis, Luke’s
physicians added ruxolitinib to his treatment regimen. After
several months of combination therapy, no leukemia cells
with the GOLGA5-JAK2 fusion protein were detectable in
Luke’s bone marrow, making him eligible to receive other
treatments to maintain long-term remission.
Researchers estimate that 23,770 new cases of brain
and other nervous system cancers will be diagnosed
in the United States in 2016, and that there will be
16,050 deaths from these types of cancers ( 3).
There are many types
of brain and central
nervous system tumors.
Most oncologists use
the World Health
classification system to identify which of the many
types of brain tumors a patient has. This information
is vital to physicians and their patients as they
understand the patient’s outlook and decide which
treatments are the best options.
The previous classification
system was based on
identifying the cell type in
which the tumor arose and
how closely the cancer cells
resemble the cell of origin ( 104).
The new classification
system integrates molecular
information about a patient’s
tumor with information on
the cell of origin and how
the cells look compared with
the cell of origin ( 103). This
reclassification was made
possible by research that
revealed the genetic and
epigenetic variability among
tumors previously thought
to be of the same type.
OF BRAIN TUMORS
In May 2016, the WHO updated the brain and
central nervous system tumor classification
system ( 103).
The new classification system will allow physicians
to more precisely diagnose and treat patients.
As of July 31, 2016, breakthrough
therapy designation has
been awarded to
anticancer therapeutics since its
introduction in 2012; 18 of these
have received FDA approvals
after being designated