Hi,

Maybe current predictions for CTC (or ctDNA, ctRNA) are not very optimistic because some technical reasons .... see conclusions from papers cited below:

"CTCs are defined as tumour cells that originate from primary tumours, recurrences, or metastases, circulate freely in the peripheral blood, and possess antigenic and genetic tumour-specific characteristics (...) Despite huge endeavours, detection of CTCs is still technically challenging. This is mainly due to their paucity, plasticity, and genotypic and phenotypic alterations (...), which might be caused by multiple intrinsic and extrinsic factors."

https://www.annalsofoncology.org/action/showPdf?pii=S0923-7534%2819%2934799-4

" CTCs as real-time liquid biopsy represents a promising approach for personalized treatment in oncology. The generalized use of CTCs in the daily clinical practice is not yet a reality, and it has been hampered in the past by their small number in the circulation, and their phenotypic changes during cancer progression. "

http://pcm.amegroups.com/article/download/5226/pdf

" (...) CTCs are rare cells which are not present in every patient, particularly so in patients with EBC. Nevertheless, there is ample evidence that CTCs—once detected—are a strong prognostic factor for reduced survival. However, at present, it is not clear how this knowledge can be transferred to a prediction of therapy response and an improved clinical outcome "

Article Are Circulating Tumor Cells (CTCs) Ready for Clinical Use in...

...... but it's a very promising idea so I believe CTC and related techniques be able to predict response to treatment very soon and be very helpful in everyday clinical practice. Now still many opent topic are discussed (see below) but trend is irreversible ...

Article ctDNA and CTCs in Liquid Biopsy – Current Status and where w...

Best regards,

Tomasz

Clinical application of Liquid Biopsy in Oncology is currently limited to Lung cancer and EGFR. Primary reason being inability to formulate guidelines based on retrieval of CTC depending upon stage of cancer, size of primary tumor and age of patient, to an extent.

Shedding of tumor DNA is not predictable so far. CHIP will interfere with results of old age patients as well.

Thank you both for your responses.

Professor Grabowski, I read the three papers you cited here. The first paper is from 2013 and therefore and these more novel technologies for CTC capture had not been developed at this time. This paper specifically refers to EpCAM-based enrichment of CTCs using CellSearch. It also states:

"Our understanding of biological characteristics of

CTCs has also been hampered by the non-availability of techniques capable of isolating them in sufficient numbers and under

conditions that are compatible with detailed molecular and

functional experiments"

This is why I'm wondering if these more novel techniques perhaps provide this opportunity. It concludes asking:

"has the time come to substitute the technique with unbiased negative selection as has been advocated or perhaps simply employ strategies that isolate CTCs based on size, density, surface charge, deformability, or other physical characteristics?"

The second paper is from 2019 and asks whether CTC usage is ready for clinical practice. It states that:

"At present, it is not clear how this knowledge can be transferred to a prediction of therapy response and an improved clinical outcome. The STIC CTC trial showed the first data for a positive effect of a CTC-based decision in a subgroup with a high count of CTCs before starting treatment. Thus, CTCs might represent a helpful early treatment monitoring tool and can be used in situations with uncertain therapy response."

However, I note all the studies included in this paper (SWOG S0500, CirCe01, STIC CTC, CirCe T-DM1, DETECT use the CellSearch EpCAM based system and do not examine the more novel technologies for CTC capture.

The final article cited here mentions the newer techniques of isolating CTCs using not just protein expression (eg. epCAM) to detect cells but also physical properties. It states that:

"The combination of different methods will most likely become the standard for single rare cell characterization in oncology."

It would appear to me therefore that these more novel technologies are indeed useful for CTC capture and may complement existing techniques?

It appears evidence is still outstanding on how these technologies be able to predict response to treatment in the near future? Are there any trials ongoing that provides fresh information?

Thank you Dr Anu for your response. Why is CTC limited to lung cancer with EGFR and have CTCs enabled treatment based on EGFR expression in these cancers? Do you think this will progress to other cancers such as breast and prostate? What does CHIP refer to in this context? I understand that tumour DNA shedding is unpredictable so perhaps this will limit the utility of ctDNA and CTC usage in clinical practice unless these techniques can be refined?

Regards,

Cormac Mullins