Current Perspectives on Circulating Tumor DNA, Precision Medicine, and Personalized Clinical Management of Cancer

Oliveira, Kelly C.S.; Ramos, Iago Barroso; Silva, Jéssica Manoelli Costa da; Barra, Williams Fernandes; Riggins, Gregory J.; Palande, Vikrant; Pinho, Catarina Torres; Frenkel‐Morgenstern, Milana; Santos, Sidney; Assumpção, Paulo Pimentel de; Burbano, Rommel Rodrı́guez; Calcagno, Danielle Queiroz

doi:10.1158/1541-7786.mcr-19-0768

Cited by 63 publications

(58 citation statements)

References 90 publications

(95 reference statements)

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“…Novel methods such as circulating tumour DNA sequencing could be utilised to avoid sampling bias and increase the number of patients for whom genomic information is available. Nevertheless there are still cases of discordance between circulating tumour DNA and tumour DNA from sequenced samples, and plasma sampling has a higher rate of false negatives [1,46]. Secondly, a panel of the size employed in this study cannot accurately estimate the true total mutation burden, and the mutation number per sample reported here cannot be considered a surrogate measure.…”

Section: Discussionmentioning

confidence: 90%

Clinical implications of prospective genomic profiling of metastatic breast cancer patients

et al. 2020

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Background: Metastatic breast cancer remains incurable. Next-generation sequencing (NGS) offers the ability to identify actionable genomic alterations in tumours which may then be matched with targeted therapies, but the implementation and utility of this approach is not well defined for patients with metastatic breast cancer. Methods: We recruited patients with advanced breast cancer of any subtype for prospective targeted NGS of their most recent tumour samples, using a panel of 108 breast cancer-specific genes. Genes were classified as actionable or non-actionable using the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines. Results: Between February 2014 and May 2019, 322 patients were enrolled onto the study, with 72% (n = 234) of patients successfully sequenced (n = 357 samples). The majority (74%, n = 171) of sequenced patients were found to carry a potentially actionable alteration, the most common being a PIK3CA mutation. Forty-three percent (n = 74) of patients with actionable alterations were referred for a clinical trial or referred for confirmatory germline testing or had a change in therapy outside of clinical trials. We found alterations in AKT1, BRCA2, CHEK2, ESR1, FGFR1, KMT2C, NCOR1, PIK3CA and TSC2 to be significantly enriched in our metastatic population compared with primary breast cancers. Concordance between primary and metastatic samples for key driver genes (TP53, ERBB2 amplification) was > 75%. Additionally, we found that patients with a higher number of mutations had a significantly worse overall survival. Conclusion: Genomic profiling of patients with metastatic breast cancer can have clinical implications and should be considered in all suitable patients.

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Section: Discussionmentioning

confidence: 90%

Clinical implications of prospective genomic profiling of metastatic breast cancer patients

et al. 2020

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“…In 2016, the cobas EGFR mutation test 2 (Roche Molecular Systems), which is capable of detecting 42 different EGFR mutations in exons 18-21 in tissue-derived as well as plasma-derived DNA, received the FDA approval. The study of the use of this test in the NSCLC patients enrolled in the ENSURE trial concluded that ctDNA assay could be recommended as a suitable alternative to tissue biopsy analysis for the assessment of EGFR mutational status [107,108]. Importantly, the Liquid Long-O-Cohort trial involving the evaluation of the efficacy of Osimertinib through ctDNA analysis of NSCLC patients using the Cobas EGFR mutation test 2 recommended ctDNA analysis as a feasible alternative to tumor biopsies for the screening of acquired EGFR T790M resistance mutation [105].…”

Section: Lung Cancermentioning

confidence: 99%

“…Certain clinical trials currently under progress, such as the MELROSE phase II trial, have included ctDNA analysis as a tool for evaluating the genetic tumor profile at the time of disease progression in the NSCLC patients undergoing treatment with Osimertinib [107], while other studies have supported the capacity of ctDNA assay to detect other genetic alterations observed in NSCLC, such as ALK or ROS1 translocations [108].…”

Section: Lung Cancermentioning

confidence: 99%

Detection of Circulating Tumor DNA in Solid Tumors

Testa¹,

Castelli²

2020

genetics

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Cancer is characterized by sequential and progressive genetic and epigenetic alterations in key proto-oncogenes and tumor suppressor genes, which ultimately lead to tumor development. Advances in the technology of analysis of molecular mechanisms have increased the efficiency of clinical management of cancer patients. Recent years have witnessed a progressive development in technologies that enable the detection of specific molecular abnormalities associated with various types of solid tumors in body fluids, a process that is globally known as "liquid biopsy". Liquid biopsy is largely based on the circulating free DNA (cfDNA) present in the plasma of healthy individuals and derived either from cell apoptosis or from the active secretion of microvesicles mediated by white blood cells (WBCs). The plasma of cancer patients contains DNA, which is referred to as circulating tumor DNA (ctDNA) and is released by the tumor cells in the form of DNA fragments of various sizes bearing the various types of genetic abnormalities specific to the tumors from which were derived. Sequencing studies conducted with several thousands of cancer patients have revealed that ctDNA accounts for only a fraction of the total DNA, and the size of this fraction varies in relation to tumor burden, tumor site, tumor subtypes, and several other biological properties of the tumor cells. Therefore, the levels of ctDNA are extremely low in several earlystage tumors, requiring highly sensitive methods for the detection of genetic alterations

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“…Jeremy et al [4] has conducted a survey concerning global incidence of prostate cancer in developing and developed countries and revealed that the global incidence of prostate cancer has been increasing in most countries, especially in Asia, Northern and Western Europe [5]. Although the therapeutic strategies for prostate cancer are varied, the genetic heterogeneity among different prostate cancer patients make the precision medicine gradually important and popular in the treatment of prostate cancer [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Identification of marker genes and cell subtypes in castration-resistant prostate cancer cells

Lin¹,

Lin²,

Lin³

et al. 2021

J. Cancer

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The diverse tumor cell populations may be the critical roles in relapse and resistance to treatment in prostate cancer patients. This study aimed to identify new marker genes and cell subtypes among castration-resistant prostate cancer (CRPC) cells. We downloaded single-cell RNA seq profiles (GSE67980) from the Gene Expression Omnibus (GEO) database. Principal component (PC) analysis and t-Distributed Stochastic Neighbor Embedding (TSNE) analysis were performed to identify marker genes. CRPC cells were clustered and annotated. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses among marker genes were performed. A total of 1500 genes with larger standardized variance were obtained. The top 20 genes were demonstrated in each identified 20 PCs. PC with P-value < 0.05 was selected, including PC1, PC7, PC8, and PC14. The TSNE analysis classified cells as two clusters. The top 6 genes in cluster 0 included HBB, CCL5, SLITRK4, GZMB, BBIP1, and PF4V1. Plus, the top 6 genes in cluster 1 included MLEC, CCT8, CCT3, EPCAM, TMPRSS2, EIF4G2. The GO analysis revealed that these marker genes were mainly enriched in RNA catabolic process, translational initiation, mitochondrial inner membrane, cytosolic part, ribosome, cell adhesion molecule binding, cadherin binding, and structural constituent of ribosome. The KEGG analysis showed that these marker genes mainly enriched in metabolism associated pathways, including carbon metabolism, cysteine and methionine metabolism, propanoate metabolism, pyruvate metabolism, and citrate cycle pathways. To conclude, our results provide essential insights into the spectrum of cellular heterogeneity within human CRPC cells. These marker genes, GO terms and pathways may be critical in the development and progression of human CRPC.

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Current Perspectives on Circulating Tumor DNA, Precision Medicine, and Personalized Clinical Management of Cancer

Cited by 63 publications

References 90 publications

Clinical implications of prospective genomic profiling of metastatic breast cancer patients

Clinical implications of prospective genomic profiling of metastatic breast cancer patients

Detection of Circulating Tumor DNA in Solid Tumors

Identification of marker genes and cell subtypes in castration-resistant prostate cancer cells

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