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Cancers
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Circulating Cancer Biomarkers: Progress, Challenges and Opportunities
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Circulating Cancer Biomarkers: Progress, Challenges and Opportunities

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 7931

Special Issue Editor

Dr. Ali Zaidi

E-Mail Website
Guest Editor
Esophageal and Lung Institute, Allegheny Health Network Institute, Pittsburgh, PA 15212, USA
Interests: esophageal cancer; development therapeutics; precision medicine; lung cancer; surveillance; early detection; disease monitoring; treatment response and immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is a leading cause of morbidity and mortality worldwide. Therefore, there is an urgent to identify, develop and validate novel non-invasive cancer biomarkers for screening and early detection, risk assessment, accurate diagnosis, patient prognosis, prediction of response to therapy, and cancer surveillance and monitoring response. These markers can also be used as targets for future cancer treatments.

Currently, cancer biomarkers can be measured in both tissue and liquid biopsy and may include germline or somatic genetic variants, transcriptional changes, epigenetic, proteomic and metabolomic signatures. In recent years, tremendous advances have been made in high throughput ‘omics’ approaches, including techniques such as next-generation sequencing or methods to study circulating tumor DNA/RNA, exosomes or proteins. This progress has been most visible in the development of minimally invasive blood-based approaches to comprehensively identify and characterize molecular alterations from heterogeneous primary tumors, while simultaneously capturing tumor load and metastasis. However, challenges remain with developing new liquid biopsy biomarkers with high sensitivity, specificity, and positive predictive value, which is now being addressed through improved technology and bioinformatics.

This Special Issue will highlight the role of circulating biomarkers on cancer care, by improving cancer patient diagnoses, management, and outcomes. We welcome both original research or review articles covering basic and clinical research studies aligned with the aforementioned topic.

Dr. Ali Zaidi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liquid biopsy
  • cancer biomarkers
  • precision oncology
  • early detection
  • response monitoring
  • prognosis
  • predicting treatment response
  • risk stratification
  • screening and surveillance
  • ctDNA
  • transcriptomics
  • proteomics
  • DNA methylation
  • metabolomics
  • genomics

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Published Papers (5 papers)

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Research

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13 pages, 3203 KiB  
Article
Fecal Microbiome Composition Correlates with Pathologic Complete Response in Patients with Operable Esophageal Cancer Treated with Combined Chemoradiotherapy and Immunotherapy
by Fyza Y. Shaikh, Seoho Lee, James R. White, Yujie Zhao, Jacqueline T. Ferri, Gavin Pereira, Blair V. Landon, Suqi Ke, Chen Hu, Josephine L. Feliciano, Russell K. Hales, K. Ranh Voong, Richard J. Battafarano, Stephen C. Yang, Stephen Broderick, Jinny Ha, Elizabeth Thompson, Eun J. Shin, David L. Bartlett, Benny Weksler, Drew M. Pardoll, Valsamo Anagnostou, Vincent K. Lam, Ali H. Zaidi, Ronan J. Kelly and Cynthia L. Searsadd Show full author list remove Hide full author list
Cancers 2024, 16(21), 3644; https://doi.org/10.3390/cancers16213644 - 29 Oct 2024
Viewed by 244
Abstract
Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The [...] Read more.
Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer. Methods: Fecal and tumor samples were collected from patients with stage II–III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function. Results: The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray–Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, including Streptococcus and Veillonella. Conclusions: These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI. Full article
(This article belongs to the Special Issue Circulating Cancer Biomarkers: Progress, Challenges and Opportunities)
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16 pages, 4089 KiB  
Article
Programmed Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor and Monitor of Response to Atezolizumab plus Bevacizumab Treatment in Patients with Hepatocellular Carcinoma
by Takuto Nosaka, Yosuke Murata, Yu Akazawa, Tomoko Tanaka, Kazuto Takahashi, Tatsushi Naito, Hidetaka Matsuda, Masahiro Ohtani, Yoshiaki Imamura and Yasunari Nakamoto
Cancers 2024, 16(9), 1785; https://doi.org/10.3390/cancers16091785 - 6 May 2024
Cited by 1 | Viewed by 1834
Abstract
There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable the serial collection of living tumor cells. Pre-treatment and serial CTC gene expression changes and tumor histology were [...] Read more.
There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable the serial collection of living tumor cells. Pre-treatment and serial CTC gene expression changes and tumor histology were evaluated to identify predictors of response to Atezo/Bev. Peripheral blood from 22 patients with HCC treated with Atezo/Bev and 24 patients treated with lenvatinib was serially collected. The RNA expression in CTCs was analyzed using qRT-PCR. Higher PD-L1 expression in pre-treatment CTCs was associated with response and improved prognosis with Atezo/Bev treatment, but not with lenvatinib. There was no correlation between PD-L1 expression in CTCs and that in liver tumor biopsy specimens scored using imaging software. Furthermore, PD-L1 RNA expression in CTCs was dynamically altered by Atezo/Bev, decreasing during effective response and increasing upon progression. CTC-derived RNA collected during Atezo/Bev indicates that patients with higher PD-L1 expression in CTCs at baseline were 3.9 times more responsive to treatment. Therefore, PD-L1 RNA levels in CTCs are an accurate response predictor and may be a monitorable biomarker that changes dynamically to reflect the response during Atezo/Bev treatment. Full article
(This article belongs to the Special Issue Circulating Cancer Biomarkers: Progress, Challenges and Opportunities)
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15 pages, 6493 KiB  
Article
Modeling the Effect of Spatial Structure on Solid Tumor Evolution and Circulating Tumor DNA Composition
by Thomas Rachman, David Bartlett, William LaFramboise, Patrick Wagner, Russell Schwartz and Oana Carja
Cancers 2024, 16(5), 844; https://doi.org/10.3390/cancers16050844 - 20 Feb 2024
Cited by 1 | Viewed by 1833
Abstract
Circulating tumor DNA (ctDNA) monitoring, while sufficiently advanced to reflect tumor evolution in real time and inform cancer diagnosis, treatment, and prognosis, mainly relies on DNA that originates from cell death via apoptosis or necrosis. In solid tumors, chemotherapy and immune infiltration can [...] Read more.
Circulating tumor DNA (ctDNA) monitoring, while sufficiently advanced to reflect tumor evolution in real time and inform cancer diagnosis, treatment, and prognosis, mainly relies on DNA that originates from cell death via apoptosis or necrosis. In solid tumors, chemotherapy and immune infiltration can induce spatially variable rates of cell death, with the potential to bias and distort the clonal composition of ctDNA. Using a stochastic evolutionary model of boundary-driven growth, we study how elevated cell death on the edge of a tumor can simultaneously impact driver mutation accumulation and the representation of tumor clones and mutation detectability in ctDNA. We describe conditions in which invasive clones are over-represented in ctDNA, clonal diversity can appear elevated in the blood, and spatial bias in shedding can inflate subclonal variant allele frequencies (VAFs). Additionally, we find that tumors that are mostly quiescent can display similar biases but are far less detectable, and the extent of perceptible spatial bias strongly depends on sequence detection limits. Overall, we show that spatially structured shedding might cause liquid biopsies to provide highly biased profiles of tumor state. While this may enable more sensitive detection of expanding clones, it could also increase the risk of targeting a subclonal variant for treatment. Our results indicate that the effects and clinical consequences of spatially variable cell death on ctDNA composition present an important area for future work. Full article
(This article belongs to the Special Issue Circulating Cancer Biomarkers: Progress, Challenges and Opportunities)
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13 pages, 6021 KiB  
Communication
Navigating Precision Oncology: Insights from an Integrated Clinical Data and Biobank Repository Initiative across a Network Cancer Program
by Bibek Aryal, Zhadyra Bizhanova, Edward A. Joseph, Yue Yin, Patrick L. Wagner, Emily Dalton, William A. LaFramboise, David L. Bartlett and Casey J. Allen
Cancers 2024, 16(4), 760; https://doi.org/10.3390/cancers16040760 - 12 Feb 2024
Viewed by 2222
Abstract
Advancing cancer treatment relies on the rapid translation of new scientific discoveries to patient care. To facilitate this, an oncology biobank and data repository program, also referred to as the “Moonshot” program, was launched in 2021 within the Integrated Network Cancer Program of [...] Read more.
Advancing cancer treatment relies on the rapid translation of new scientific discoveries to patient care. To facilitate this, an oncology biobank and data repository program, also referred to as the “Moonshot” program, was launched in 2021 within the Integrated Network Cancer Program of the Allegheny Health Network. A clinical data program (CDP) and biospecimen repository were established, and patient data and blood and tissue samples have been collected prospectively. To date, the study has accrued 2920 patients, predominantly female (61%) and Caucasian (90%), with a mean age of 64 ± 13 years. The most common cancer sites were the endometrium/uterus (12%), lung/bronchus (12%), breast (11%), and colon/rectum (11%). Of patients diagnosed with cancer, 34% were diagnosed at stage I, 25% at stage II, 26% at stage III, and 15% at stage IV. The CDP is designed to support our initiative in advancing personalized cancer research by providing a comprehensive array of patient data, encompassing demographic characteristics, diagnostic details, and treatment responses. The “Moonshot” initiative aims to predict therapy responses and clinical outcomes through cancer-related biomarkers. The CDP facilitates this initiative by fostering data sharing, enabling comparative analyses, and informing the development of novel diagnostic and therapeutic methods. Full article
(This article belongs to the Special Issue Circulating Cancer Biomarkers: Progress, Challenges and Opportunities)
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13 pages, 1729 KiB  
Review
Defensins: Exploring Their Opposing Roles in Colorectal Cancer Progression
by Hussein Sabit, Timothy M. Pawlik, Shaimaa Abdel-Ghany and Borros Arneth
Cancers 2024, 16(15), 2622; https://doi.org/10.3390/cancers16152622 - 23 Jul 2024
Cited by 1 | Viewed by 1193
Abstract
Colorectal cancer (CRC) represents a significant global healthcare burden, with a particularly concerning rising incidence among younger adults. This trend may highlight potential links between diet, gut microbiome, and CRC risk. Novel therapeutic options have been increasingly based on the understanding of molecular [...] Read more.
Colorectal cancer (CRC) represents a significant global healthcare burden, with a particularly concerning rising incidence among younger adults. This trend may highlight potential links between diet, gut microbiome, and CRC risk. Novel therapeutic options have been increasingly based on the understanding of molecular mechanisms and pathways. The PI3K/AKT/mTOR pathway, a crucial cell growth regulator, offers a promising target for CRC therapy. mTOR, a key component within this pathway, controls cell growth, survival, and metabolism. Understanding the specific roles of defensins, particularly human β-Defensin 1 (HBD-1), in CRC is crucial. HBD-1 exhibits potent antimicrobial activity and may influence CRC development. Deciphering defensin expression patterns in CRC holds the promise of improved understanding of tumorigenesis, which may pave the way for improved diagnostics and therapies. This article reviews recent advances in understanding regarding how HBD-1 influences CRC initiation and progression, highlighting the molecular mechanisms by which it impacts CRC. Further, we describe the interaction between defensins and mTOR pathway in CRC. Full article
(This article belongs to the Special Issue Circulating Cancer Biomarkers: Progress, Challenges and Opportunities)
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