Dataset Information

Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics.

ABSTRACT: Bi-directional crosstalk between the tumor and the tumor microenvironment (TME) has been shown to increase the rate of tumor evolution and to play a key role in neoplastic progression, therapeutic resistance, and a patient's overall survival. Here, we set out to use a comprehensive liquid-biopsy analysis to study cancer and specific TME cells in circulation and their association with disease status. Cytokeratin+, CD45- circulating rare cells (CRCs) from nine breast and four prostate cancer patients were characterized through morphometrics, single-cell copy number analysis, and targeted multiplexed proteomics to delineate cancer cell lineage from other rare cells originating in the TME. We show that we can detect epithelial circulating tumor cells (EPI.CTC), CTCs undergoing epithelial-to-mesenchymal transition (EMT.CTC) and circulating endothelial cells (CECs) using a universal rare event detection platform (HDSCA). Longitudinal analysis of an index patient finds that CTCs are present at the time of disease progression, while CECs are predominately present at the time of stable disease. In a small cohort of prostate and breast cancer patients, we find high inter-patient and temporal intra-patient variability in the expression of tissue specific markers such as ER, HER2, AR, PSA and PSMA and EpCAM. Our study stresses the importance of the multi-omic characterization of circulating rare cells in patients with breast and prostate carcinomas, specifically highlighting overlapping and cell type defining proteo-genomic characteristics of CTCs and CECs.

SUBMITTER: Welter L

PROVIDER: S-EPMC10417732 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics.

Welter Lisa L Zheng Serena S Setayesh Sonia Maryam SM Morikado Michael M Agrawal Arushi A Nevarez Rafael R Naghdloo Amin A Pore Milind M Higa Nikki N Kolatkar Anand A Thiele Jana-Aletta JA Sharma Priyanka P Moore Halle C F HCF Richer Jennifer K JK Elias Anthony A Pienta Kenneth J KJ Zurita Amado J AJ Gross Mitchell E ME Shishido Stephanie N SN Hicks James J Velasco Carmen Ruiz CR Kuhn Peter P

Cancers 20230803 15

Bi-directional crosstalk between the tumor and the tumor microenvironment (TME) has been shown to increase the rate of tumor evolution and to play a key role in neoplastic progression, therapeutic resistance, and a patient's overall survival. Here, we set out to use a comprehensive liquid-biopsy analysis to study cancer and specific TME cells in circulation and their association with disease status. Cytokeratin+, CD45- circulating rare cells (CRCs) from nine breast and four prostate cancer patie ...[more]

PMID: 37568766

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Project description:Cholangiocarcinoma is a very heterogenous cancer and "target-rich" disease. While the current classifications are based on the anatomic location of these tumors (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer), tumors within and across these disease groups have unique and often mutually exclusive molecular aberrations. Amongst these, fibroblast growth factor receptor 2 (FGFR2) fusion is one of the first amongst the list of "actionable" targets for which the US Food and Drug Administration just approved pemigatinib. This is for patients with cholangiocarcinoma who have received prior treatment and have FGFR2 fusion or another rearrangement. This was based on the results from the clinical trial FIGHT-202 (NCT02924376). At present, several FGFR inhibitors are actively being tested in several agnostic and tumor-specific clinical trials. Patients also have had the opportunity of getting access to some of these oral drugs through compassionate use programs. As a consequence, these patients have more options in addition to chemotherapy. These all tend to have "good" initial responses and improvement in performance status and later "acquired" mechanisms of resistance. The latter tend to often be gatekeeper mutations that bypass the inhibitory effects of these selective FGFR inhibitors and/or cause steric hindrance. These tumors, therefore, evolve on selective pressure (temporal heterogeneity). This can be captured noninvasively using "liquid biopsies" (circulating tumor DNA testing). Here we present cases (several years into treatment on average) showing the feasibility of using liquid biopsies (ctDNA testing) as well as the gain and later potential loss of intratumoral and temporal heterogeneity exhibited under selective pressure of these novel FGFR inhibitors, chemotherapy and/or locoregional therapies. Despite limitations in sample size and provider bias, it is important to identify these "exceptional responders" and/or better outcomes that may be inherent to the biology of FGFR fusion-positive cholangiocarcinomas.

Dataset Information

Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics.

Publications

Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics.

Similar Datasets

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