Page 235 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

234 CHAPTER 9 Application of microfluidics in cancer treatment

can be achieved by understanding organ-specific interactions. Now, microfluidics is
the most appropriate in vitro systems that mimic organ-specific environments since
they exactly control the spatial distribution of different cell types mimicking the in
vivo settings. To date, studies have added organ-specific cell types or chemokines to
microfluidic models and replicated certain aspects of organ architecture [57]. In this
context, these models such as the addition of different immune cells for studying
their role in metastasis are developed [21]. Newly, reducing metastasis in melanoma
or kidney cancer patients is reported by using immunotherapies [58].
Tissue biopsy and rebiopsy used to cancer diagnosis and metastasis monitoring
until now is a very invasive procedure that is limited only to certain locations and
not always possible in clinical practice [59]. It is difficult or impossible to obtain the
tissue sample through tissue biopsy in some cases as well. Information about a very
small area of tumor is yielded at extraction time by tissue biopsy [59]. It can pose a
risk to the patient because of invasive nature and it has significant cost [60].
There is another problem that biopsies usually suffer from sample bias due to
heterogeneity of tumor and is caused false diagnosis and it is the main reason for the
failure of cancer treatment because of incapability to capture the heterogeneity dur-
ing tumor development. Tumors are dynamic and their mutation pattern changes that
resists nonspecific treatment and it causes problems to patients undergoing targeted
therapies. Liquid biopsy is a new diagnostic concept which can help to eliminate
these problems. By this method, the circulating tumor cells (CTC) and cell-free cir-
culating tumor DNA (ctDNA or cfDNA) released into the peripheral blood during
metastasis in terms of therapeutic targets and drug resistance-conferring gene muta-
tions is analyzed.
Liquid biopsy can be used as a cancer diagnostic toolkit which provides an oppor-
tunity for screening, monitoring, and treatment response and recurrence detection
after surgery [61]. Undoubtedly, liquid biopsy is a valuable addition to the oncolo-
gist’s tool because it improves disease monitoring over time and avoids painful pro-
cedures such as conventional tissue biopsy and radiological assessment. As well, in
order to tumor burden monitoring in the blood and early detection of emerging resis-
tance of targeted cancer therapies, liquid biopsy can be used. Circulating tumor cells
(CTCs), a component of the “liquid biopsy”, are generally accepted as an indicator
for early cancer diagnosis [62]. Many new technologies have been developed to the
detection of CTCs in the peripheral blood of patients with solid epithelial tumors
(e.g., breast, prostate, lung, and colon cancer). Detection of CTCs has been exten-
sively reported in various metastatic cancers including breast, prostate, lung, and
colorectal cancers. Recent research demonstrates, because of the existence of the sig-
nificant relation between CTC enumeration and prognosis of cancer patients, CTCs
are either surrogate of the metastatic activity or causally involved in the metastatic
process [59]. Dielectrophoresis technic is another method, based on hydrodynamic
flow, that has been used for target CTCs separation. In this method, dielectric forces
apply through microelectrode arrays and cells that get separated based on similar
properties [63]. The efficiency of this method was reported by more than 90%. In
addition, blood flow should be slow in this method, and being in an isotonic medium