Page 58 - Read Online

discovered in patients, whose primary tumor is KRAS Casavant et al. provides signifi cant data of study on
[93]
wild type. An ultra-deep sequencing revealed the presence animal models demonstrating use of CTCs in SCLC as
of KRAS mutated group of cells in the primary tumor. “liquid biopsy” and paving way for personalized medicine.
This is another example revealing the crucial importance The most common methods used for isolating CTCs in
of CTCs sequencing which helps us fi nd out details of the lung cancer are CellSearch and ISET kits. Both these
®
heterogeneity in the tumor which is otherwise not possible methods indicate a higher number of isolation of CTCs in
by single biopsy. CTCs have been directly related to state SCLC than NSCLC. Taenzer et al. have explained this
[92]
to disease and predicting treatment outcome in CRCs just by the possibility of EMT in NSCLC, which makes the
like other cancers. Individual markers such as KRT19, disseminated cells escape EpCAM selection. Mutations on
MUC1, EpCAM, CEACAM5, and BIRC5 are studied exon 19 and 21 of EGFR are the prime target of drug-based
by de Albuquerque et al. showing positively ranging therapies. Other mutations such as T790M, EML4-ALK
between 15% and 35%. They have observed a shorter rearrangement, BRAF, KRAS, HER2, PIK3CA/AKT1,
progression-free survival in patients showing more of ROS, FGFR1, and MET are also of greater interest in lung
these CTCs compared to the group of patients with lesser cancer as clinical trials are now focused on mutation based
or no CTCs. In an interesting study by Allen et al., therapies. [95,96] Molecular characterization of CTCs holds
[88]
[89]
we come across the fi nding that CRC tumor-associated great importance as it can provide a very plausible means
events such as apoptotic CTCs and CTCs debris are of mutation detection. Furthermore, one can be easily
more indicative of liver metastasis in particular than just monitored periodically for the development of any resistant
CTCs count. These events are more indicative of the site mutations during the course of treatment. [97-99] Higher
of metastasis rather than primary tumor and hence are number CTCs in lung cancer has been associated with larger
clinically very signifi cant. CRC has often been related tumor size and in particular in bone metastasis. [100-102] CTCs
[20]
to liver metastasis in particular. This is supported by have surely gathered lot of enthusiasm and effort towards
detection of increased number of CTCs in mesenteries their research with their staggering clinical potentials. But
than peripheral blood. Though the prognostic value of till date research on them has been limited by many factors,
these CTCs has not yet been validated. Denève et al. such as their small capture number being a major problem.
[90]
in their studies strongly support that liver is the fi lter site Kolostova et al. have drawn an attractive protocol
[35]
for CTCs and that viable CRC disseminated cells can be for isolation and culturing in vitro CTCs of human lung
isolated from hepatic tissue. Reports are pointing out that cancer. If CTCs can be cultured in vitro like other cells,
the EpCAM+ CTCs are often detected in liver indicating it will be of great benefi cial value as it will pace up the
a strong signal of association of liver metastasis in CRC. investigation on the nature of CTCs and its characterization.
In another study by Antolovic et al. have noted worse Furthermore, circulating tumor micro-emboli (CTMs) have
[91]
overall survival in later stages of CRC patient-derived been reported in many cases of lung cancer. CTMs are
CTCs having CEA/CK/CD133 positive mRNA than those cluster of disseminated tumor cells in circulation. CTM are
who are negative for these markers. They have discussed of particular interest in this case as they are considered to
about use of additional markers like CD133 for detection be markers of extreme metastatic potential. [103] Treatment
of not only CK20+ and CEA+ subpopulation of CTCs but response is a major question in advanced lung cancer. CTCs
also for more aggressive type CD133+ disseminated cells. count can potentially help approve the ongoing treatment
Improvements in the detection of CTCs continue to and also help in suggesting any alterations if required. [104,105]
evolve as the need does. In one study Antolovic et al. Ilie et al. [105] in their discussion on CTCs in lung cancer have
[91]
have suggested the use of Ficoll gradient isolation prior indicated possibilities of the presence of these cells even
to use of EpCAM enrichment technique of CTCs for before angiogenesis. CTCs can be present in circulation long
enhanced results. In many cases, it is easier for clinicians time before the disease can be actually detected. Therefore,
to treat a suffering patient if the malignancy is detected they can become the core of research in regards of early
earlier. Hence, in cases such as that of CRC where early detection of the disease for symptomatic patients. [106-108]
detection still awaits some effi cient technique, CTCs
can play a good enough role in not only detecting and CTCs in Other Cancers Diagnosis and
personifying but also providing a real-time means of the Treatment
disease status along the treatment journey. CTCs can be detected in almost all of the solid tumor
malignancies and changes in the disease state can be
CTCs in Lung Cancer Diagnosis and Treatment
predicted with the help of CTCs. Genes like VIM,
Lung cancer is broadly classifi ed as small cell TGFBR2, TGFB, and SERPINE1 which are indicative of
lung cancer (SCLC) and non-SCLC (NSCLC). Early mesenchymal phenotype, are expressed in higher levels
detection continues to remain a challenge in lung in the CTCs of glioblastoma cancer in comparison to the
cancer, reducing the chances of survival. Dissemination is cells of the primary tumor or cell culture. [109-111] TWIST
an early event in both these types of lung cancer and hence and Vimentin are considered as diagnostic markers
CTCs can be of great use in lung cancer as the available for hepatocellular carcinoma. TWIST is known to
biopsies are not readily procurable. [92-94] A study by suppress expression of E-cadherin while overexpression
Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦ 51