Liquid biopsies to enable non-invasive real-time functional chemoresistance profiling in solid organ cancers

Autor: Sewanti Limaye, Rajan Datar, S. Pawar, Ashok Gawai, Darshana Patil, Cynthe Sims, Stefan Schuster, Tim Crook, Vineet Datta, Raymond L. Page, Ajay Srinivasan, Sachin Apurwa, Vishakha Mhase, Dadasaheb Akolkar, Harshal Bodke, Sanket Patil
Rok vydání: 2020
Předmět:
Zdroj: Journal of Clinical Oncology. 38:3525-3525
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2020.38.15_suppl.3525
Popis: 3525 Background: Despite the development of targeted therapy agents and immune checkpoint inhibitors (ICI), cytotoxic anticancer agents remain the mainstay of treatment in several solid organ cancers. However, instances of innate and acquired resistance towards these anticancer agents can lead to treatment failures, which remain undetectable until clinical or radiological manifestation of symptoms suggestive of disease progression. There are presently no viable means or markers to detect or monitor for chemoresistance in real time. Owing to this unmet need, cancer treatment strategies face risks of failure and poor outcomes. Methods: We obtained 15 mL blood from 3,662 patients with various solid organ cancers, of various states and including treatment-naïve and pretreated patients. Circulating Tumor Associated Cells (C-TACs) were enriched and harvested from PBMCs using an epigenetically activating medium that is cytotoxic towards non-malignant epithelial and hematolymphoid cells in blood, but confers survival benefit on apoptosis resistant cells of tumorigenic origin (Circulating Tumor Associated Cells, C-TACs). In a subset of patients, fresh tumor tissue was also obtained from which viable tumor derived cells (TDCs) were obtained. Viable TDCs and C-TACs were treated with a panel of anticancer agents and the surviving cell fraction estimated to determine chemoresistance. Results: Among the 1,325 therapy naïve patients, resistance towards treatment agents was observed in C-TACs from 56.3 % of samples. Among 2,201 pretreated patients’ samples, resistance towards treatment agents was observed in C-TACs from 77.8% of samples. The increased resistance in C-TACs from pretreated patients indicated that the C-TACs had been resistance-educated by prior therapies. In a subset of patients, Chemoresistance profile of C-TACs was observed to be 96.9% concordant with that of tumor derived cells (TDCs) which were concurrently obtained from tumor tissue indicating that C-TACs accurately represent chemo-antecedents of the tumor. Conclusions: Non-invasive chemoresistance profiling of C-TACs is a viable strategy to monitor treatment efficacy in real time. Adoption of this strategy in the clinic will not only guide treatment selection with reduced risk of failure, but will also enable timely therapeutic course correction upon detection of acquired chemoresistance.
Databáze: OpenAIRE
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