Page 59 - Read Online
P. 59
of Vimentin is strongly related with the mesenchymal
phenotype of these CTCs. Overexpression of ZEB1
and ZEB2 is also reported in this cancer. [112] So far, no
specifi c marker has been reported for bladder cancer.
However, it has been suggested that overexpression of
H-RAS oncogene and mutations in FGR-R genes in CTCs
could be considered as a diagnostic tool. [113] Apart from
genes, other cellular transformations like loss of cellular
junctions which aid in cell to cell communications are
indicative of mesenchymal phenotype. Markers such as
CK20, UP II, and EGFR have been related to diagnosis
of bladder cancer. CTCs can be assessed to detect the
presence of these markers and aid in the diagnosis of
[41]
the malignancy. [114,115] Alonso-Alconada et al. have done
molecular profi ling of CTCs isolated from metastatic Figure 5: Size-based separation of circulating tumor cells
endometrial carcinoma (EC) patients. They have shown
that there is an overexpression of stem cell related genes, numbers has limited research. We anticipate the
i.e. ALDH and CD44, EC related genes such as BRAF, development of isolation and enrichment combination
PIK3CA, RELA, RUNX1, and EMT related genes, that techniques which help in avoiding cell loss. A range of
is, ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 in these specifi c markers is also bound to enhance the enrichment
patients. Of these genes, ETV5, in particular, is strongly results as those cells which can escape EpCAM selection
[41]
related to increased metastasis and CTCs plasticity. could also be captured. Given their tremendous potential
[41]
Häfner et al. [116] have shown that the evaluation of level to help change the enigmatic situation of solid tumors, we
of HPV16-E6 mRNA by real-time PCR is more sensitive can conclude that CTCs are sure to become an inevitable
molecular marker expressed in CTCs isolated from part in the near future of solid tumors malignancies.
metastatic cervical cancer patients than that of commonly
used CK19 mRNA as a marker. Just like other solid Acknowledgments
tumors, in case of pancreatic cancer, several studies
have similarly suggested the use of CTCs for not only Authors wish to acknowledge Management of Jaslok Hospital
diagnosing but also for identifying metastasis in patients and Research Centre, Mumbai for providing facilities to
and helping to select patient-specifi c therapies. [117-119] A establish CSC laboratory in the Department of Molecular
study by Kuhlmann et al. [120] brings to light an importance Medicine and Biology. This gave an excellent exposure to
of the molecular characterization of CTCs in ovarian develop this important technology in this laboratory and thus to
cancer. They have shown that ERCC1+ CTCs can predict write such an important review on this topic.
platinum resistance therapy in ovarian cancer which is References
still remains a big challenge in the treatment of ovarian
malignancy. [120] Obermayer et al. [121] have shown that there 1. Gavhane YN, Shete AS, Bhagat AK, Shinde VR, Bhong KK,
are more number of cyclophilin C gene (PPIC) positive Khairnar GA, Yadav AV. Solid tumors: facts, challenges and
CTCs are detected usually in ovarian platinum-resistant 2. solutions. Int J Pharm Sci Res 2011;2:1-12. MJ, Siu LL.
Bedard
PL,
Hansen
AR,
Ratain
cancer group as compared to the sensitive group than Tumorheterogeneity in the clinic. Nature 2013;501:355-64.
EpCAM positive CTCs in these patients. It is also related 3. Greaves M, Maley CC. Clonal evolution in cancer. Nature
to poor outcomes of this disease. [121] Advancements in 2012;481:306-13.
CTCs detection techniques have given rise to newer 4. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG.
methods, such as the one-step detection of using Cancer drug resistance: an evolving paradigm. Nat Rev
fl uorescent silica nanoparticles for ovarian cancer. [122] With Cancer 2013;13:714-26.
the growing technologies and persistent work on CTCs, 5. Bogenrieder T, Herlyn M. Axis of evil: Molecular mechanisms
we are slowly channelizing the efforts to derive a clearer of cancer metastasis. Oncogene 2003;22:6524-36.
picture of the use of CTCs in diagnosis and treatment of 6. Kleiner DE, Stetler-Stevenson WG. Matrix metalloproteinases and
metastasis. Cancer Chemother Pharmacol 1999;43 Suppl: S42-51.
various cancers. 7. Chaffer CL, Weinberg RA. A perspective on cancer cell
metastasis. Science 2011;331:1559-64.
Future Directions
8. Micalizzi DS, Farabaugh SM, Ford HL. Epithelial-mesenchymal
Taken together, CTCs have potential to aid in the transition in cancer: parallels between normal development
entire course of a patient’s cancer journey starting from and tumour progression. J Mammary Gland Biol Neoplasia
2010;15:117-34.
diagnosis, treatment selection, post-treatment/surgery 9. Carmeliet P, Jain RK. Angiogenesis in cancer and other
monitoring, and follow-up. Although vast amount of diseases. Nature 2000;407:249-57.
research have been accelerated in the fi eld of these 10. Yap TA, Lorente D, Omlin A, Olmos D, de Bono JS.
disseminated tumor cells, their availability in scant Circulating tumour cells: a multifunctional biomarker. Clin
52 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦