ALK gene mutations fuel 3 to 7 percent of NSCLCs (138).
Although crizotinib benefits many patients with NSCLC
driven by ALK, not all patients respond. Moreover, the
majority of patients who initially respond to crizotinib
treatment eventually relapse because the cancer becomes
resistant to the ALK-targeted therapeutic (138).
One cause of crizotinib resistance is the emergence of new
mutations in ALK. Alectinib is able to block many of the
unique forms of ALK that result from these new mutations
and in phase I/II clinical trials, treatment with alectinib
caused tumor shrinkage or disappearance in patients with
crizotinib-resistant NSCLC driven by ALK. Alectinib
was even able to shrink tumors that had metastasized to
the brain, which is something the other ALK-targeted
therapeutics are less able to do (138). It is hoped that future
studies will show that alectinib also improves survival for
patients with ALK-fueled NSCLC.
About 1 percent of patients with NSCLC have tumors that
are fueled by mutations in the ROS1 gene, which generates
a protein that is related to ALK (139). In March 2016, the
FDA approved crizotinib for treating patients with ROS1-
fueled NSCLC after a phase I clinical trial showed that the
anticancer therapeutic caused partial or complete tumor
shrinkage in patients with this type of NSCLC (139). This
new approval both expands the number of patients with
NSCLC who may benefit from crizotinib and increases
the return on prior investments in biomedical research.
Most patients with EGFR-mutant NSCLC have the
nonsquamous cell type of NSCLC (140). Even though
EGFR mutations are rarely detected in the less common
squamous cell type of NSCLC, most of these cancers have
elevated levels of EGFR protein on their surface (140). This
observation suggested to researchers that EGFR-targeted
therapeutics might benefit patients with squamous NSCLC.
are stringently tested for
by the U. S.
Food and Drug
accurately match patients with
the most appropriate therapy;
allow patients to receive a
treatment to which they are
most likely to respond; and
allow patients identified as very
unlikely to respond to forgo
treatment with the therapeutic
and thus be spared any adverse
The effective therapeutic use of precision
medicines targeting particular cancer-driving
molecular abnormalities often requires
tests called companion diagnostics.
Adapted from ( 1)
ALK-targeted therapeutics have
been approved by the FDA for
patients with ALK mutation–fueled
NSCLC: crizotinib, ceritinib,