Prognostic value of plasma circulating tumor DNA fraction across four common cancer types: a real-world outcomes study

Reichert, Zachery R.; Morgan, Todd M.; Li, G.; Castellanos, Emily; Snow, Tamara; Dall’Olio, Filippo Gustavo; Madison, Russell; Fine, Alexander D.; Oxnard, Geoffrey R.; Graf, Ryon P.; Stover, Daniel G.

doi:10.1016/j.annonc.2022.09.163

Cited by 87 publications

(45 citation statements)

References 36 publications

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“…Our review of the available literature confirmed the potential of liquid biopsy in managing advanced BC treated with novel agents, similar to the results achieved by liquid biopsy when applied to other cancers and in other settings [ 73 ]. Liquid biopsy is critical for the study of cancer dynamics in a way that accounts for cancer heterogeneity, which is a key aspect in the metastatic setting that cannot be fully encompassed by the genomic or proteomic profile of a single metastatic site.…”

Section: Discussionsupporting

confidence: 79%

Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration

Krasniqi

Goeman

Pulito

et al. 2022

IJMS

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New evidence on the impact of dysregulation of the CDK4/6 pathway on breast cancer (BC) cell proliferation has led to the development of selective CDK4/6 inhibitors, which have radically changed the management of advanced BC. Despite the improved outcomes obtained by CDK4/6 inhibitors, approximately 10% of tumors show primary resistance, whereas acquired resistance appears to be an almost ubiquitous occurrence, leading to treatment failure. The identification of differentially expressed genes or genomic mutational signatures able to predict sensitivity or resistance to CDK4/6 inhibitors is critical for medical decision making and for avoiding or counteracting primary or acquired resistance against CDK4/6 inhibitors. In this review, we summarize the main mechanisms of resistance to CDK4/6 inhibitors, focusing on those associated with potentially relevant biomarkers that could predict patients’ response/resistance to treatment. Recent advances in biomarker identification are discussed, including the potential use of liquid biopsy for BC management and the role of multiple microRNAs as molecular predictors of cancer cell sensitivity and resistance to CDK4/6 inhibitors.

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Section: Discussionsupporting

confidence: 79%

Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration

Krasniqi

Goeman

Pulito

et al. 2022

IJMS

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“…While the deep sampling in our dataset is a unique strength, we recognize that broad implementation of short interval serial biopsy is unlikely to be clinically feasible. While circulating tumor DNA is a validated prognostic and predictive marker across multiple cancers it is inherently biased toward examining tumor intrinsic genomic features and general tumor burden [82][83][84][85][86][87] . As our focus was primarily on immune cell adaptations we paired a broad (~3,000 analytes) proteomic panel to our tissue sampling in an effort to explore peripheral surrogates of tissue level changes.…”

Section: Discussionmentioning

confidence: 99%

Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor microenvironment in advanced gastric cancer: a phase II chemoimmunotherapy trial

Mehta

Min

et al. 2023

Preprint

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Adding anti-PD1 antibodies to 5-FU/platinum chemotherapy improves survival in a subset of advanced gastroesophageal adenocarcinoma (GEA) patients. Beyond PD-L1 expression and mismatch repair status we have limited insight into molecular predictors of response or the relative contribution of PD-1 blockade. We conducted an investigator sponsored phase II trial (n = 47) sequentially adding pembrolizumab to standard 5-FU/platinum in previously untreated advanced GEA (ClinicalTrials.gov:NCT04249739). With an overall response rate of 67% the activity paralleled phase III chemoimmunotherapy trials. To understand on-treatment tumor and immune adaptations patients underwent serial biopsy of the primary tumor, including baseline, after one cycle of 5-FU/platinum, and after the addition of pembrolizumab. We leveraged transcriptional profiling from 358,067 cells to identify multicellular networks of malignant, stromal, and immune cells after chemotherapy and concurrent chemoimmunotherapy. The relative usage of pro-tumor and anti-tumor interaction hubs differed between fast and slow progressing patients. Chemotherapy induced early on-treatment formation of hubs centered on tumor-reactive T-cell and M1-oriented macrophage interactions with pro-inflammatory cytokines in slow progressors. Faster progression was characterized by increased MUC5A and MSLN containing programs in tumor cells and M2-oriented macrophages with immunosuppressive stromal interactions. After adding pembrolizumab we observed increased CD8 T-cell infiltration by scRNAseq and multiplex immunofluorescence and development of an immunity hub involving co-variation of the tumor-reactive CXCL13 program and epithelial interferon-stimulated gene programs enriched in slow progressors. Together this data provides prospective evidence of differential early on-treatment evolution of the gastric immune microenvironment and nominates candidate cellular interactions for clinical targeting.

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“…Microsatellite instability (MSI) can be analyzed using cfDNA, depending on the design method of the gene panel [18]. However, since FoundationOne Liquid CDx was not designed for this purpose, MSI detected with FoundationOne Liquid CDx is also unapproved as a companion diagnostic tool in Japan.…”

Section: Cfdna and Ctdnamentioning

confidence: 99%

“…ctDNA fraction or the variant allele frequecy of ctDNA harboring a specific mutation may be used to monitor treatment response during therapy, or to detect minimally residual disease (MRD). Recently, it has also been reported that ctDNA fraction can be a good prognostic marker in 4 major types of cancer with metastasis (prostate cancer, breast cancer, nonsmallcell lung cancer, and colorectal cancer) [18]. Even in cases where the shedding of ctDNA is low, methylation status of cfDNA derived from both cancer cells and surrounding stromal cells may be informative as a biomarker, and is actively being explored in research [19].…”

Section: Cfdna and Ctdnamentioning

confidence: 99%

The Current State and Future of Plasma Cell-Free DNA Analysis in Urologic Malignancies

Akamatsu

Mizuno

Sumiyoshi

et al. 2023

Korean J Urol Oncol

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Genomic medicine based on comprehensive genomic profiling (CGP) has revolutionized cancer treatment. However, there are certain limitations to CGP based on tissue analysis. Liquid biopsy, particularly plasma cell-free DNA (cfDNA), has emerged as a less invasive source of information to complement tissue-based analysis. To use cfDNA analysis effectively in the clinical setting, it is important to know the characteristics and specific limitations of cfDNA analysis. Moreover, the utility of cfDNA testing differs between cancer types, which is not widely recognized. Furthermore, in addition to its use in CGP, there are broader applications for cfDNA testing, including its use in detecting minimal residual disease or even epigenomic profiling. In this review, we first describe the detailed characteristics of cfDNA and the limitations of cfDNA analysis, and then focus on the utility of cfDNA analysis in urologic malignancies.

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Prognostic value of plasma circulating tumor DNA fraction across four common cancer types: a real-world outcomes study

Cited by 87 publications

References 36 publications

Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration

Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration

Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor microenvironment in advanced gastric cancer: a phase II chemoimmunotherapy trial

The Current State and Future of Plasma Cell-Free DNA Analysis in Urologic Malignancies

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