Computational Systems Biology Methods and Protocols.7z

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PFS of 13.2 months in crizotinib-pretreated patients in one phase
I/II trial [75]. On April 28, 2017, brigatinib was accelerated
approval by the FDA for the treatment of patients with
ALK-positive metastatic NSCLC who have progressed on or are
intolerant to crizotinib. These second-generation inhibitors are
more potent than crizotinib. Thus, they can overcome the most
common crizotinib-resistant mutations including the L1196M gate-
keeper mutation, which are active in crizotinib-resistant tumors
without ALK resistance mutations. These second-generation inhibi-
tors are more effective than crizotinib against central nervous system
(CNS) metastases [68–71].

5 Perspective


The finding of circulating biomarkers originated from cancer lesion
in the peripheral blood is a cutting-edge scientific discovery. The
clinical application of cfDNA for diagnosis and treatment offers a
minimal invasive method to sample. However, there are still several
challenges to overcome before routine application by clinicians.
Due to the low level of cfDNA in the peripheral blood, the applica-
tion of liquid biopsy to monitor tumor progression and recurrence
is not so well. Advances in genomics approaches are essential to
enhance the specificity and sensitivity of liquid biopsy. In addition,
it is necessary to establish a standard analysis procedure of liquid
biopsy to ensure the accuracy of analysis. With the solution of these
challenges, liquid biopsy is possible to be widely used in routine
clinical application. In conclusion, cfDNA is a very promising bio-
marker for liquid biopsy. The clinical value will become much more
obvious with the exploration of cfDNA application.

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