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.References
- Allard WJ, Matera J, Miller MC, Repollet M,
Connelly MC, Rao C, Tibbe AG, Uhr JW,
Terstappen LW (2004) Tumour cells circulate
in the peripheral blood of all major carcinomas
but not in healthy subjects or patients with
nonmalignant diseases. Clin Cancer Res 10
(20):6897–6904. https://doi.org/10.1158/
1078-0432.CCR-04-0378 - Hiraiwa K, Takeuchi H, Hasegawa H,
Saikawa Y, Suda K, Ando T, Kumagai K,
Irino T, Yoshikawa T, Matsuda S, Kitajima M,
Kitagawa Y (2008) Clinical significance of cir-
culating tumour cells in blood from patients
with gastrointestinal cancers. Ann Surg Oncol
15(11):3092. https://doi.org/10.1245/
s10434-008-0122-9 - Rink M, Chun FK, Minner S, Friedrich M,
Mauermann O, Heinzer H, Huland H,
Fisch M, Pantel K, Riethdorf S (2007) Detec-
tion of circulating tumour cells in peripheral
blood of patients with metastatic breast cancer:
a validation study of the CellSearch system.
Clin Cancer Res 13(3):920–928.https://doi.
org/10.1111/j.1464-410X.2010.09562.x.- Stott SL, Lee RJ, Nagrath S, Yu M, Miyamoto
DT, Ulkus L, Inserra EJ, Ulman M, Springer S,
Nakamura Z, Moore AL, Tsukrov DI, Kemp-
ner ME, Dahl DM, Wu CL, Iafrate AJ, Smith
MR, Tompkins RG, Sequist LV, Toner M,
Haber DA, Maheswaran S (2010) Isolation
and characterization of circulating tumour
cells from patients with localized and meta-
static prostate cancer. Sci Transl Med 2
(25):25ra23-25ra23. https://doi.org/10.
1126/scitranslmed.3000403
60 Jun Li et al.