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Cancers
Special Issues
Emerging Technologies in Cancer Diagnostics and Therapeutics
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Emerging Technologies in Cancer Diagnostics and Therapeutics

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: 23 April 2024 | Viewed by 14263

Special Issue Editors

Prof. Dr. Mary Bebawy

E-Mail Website
Collection Editor
Laboratory Cancer Cell Biology and Therapeutics, Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
Interests: extracellular vesicles; cancer multidrug resistance; liquid biopsy; multiple myeloma
Dr. Michelle Hill

E-Mail Website
Co-Collection Editor
Faculty of Medicine, The University of Queensland, Herston, Brisbane, QLD 4102, Australia
Interests: membrane lipids; cell biology; subcellular omics; integrative biology; clinical proteomics; clinical lipidomics; liquid biopsy; extracellular vesicles; clinical diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The emergence of omics technologies has seen precision oncology take centre stage in the rapidly changing oncology landscape. Minimally invasive approaches for tissue sampling and diagnosis can detect disease earlier, affording improved outcomes for patients. Liquid biopsies, which probe biological fluids for components of the tumour circulome, provide simple and routine approaches to disease monitoring. Tumour-derived constituents such as circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and tumour-derived extracellular vesicles are now readily accessible analytes thanks to advances in microfluidics and advances in isolation methodologies and approaches used in biomarker profiling, which provide high-content analysis of disease characteristics, removing the need for invasive traditional approaches. Furthermore, the emergence of digital biopsies sees AI machinery entering the clinic with unsurpassed diagnostic capabilities, disrupting traditional diagnostic capabilities.

In a similar manner, advances in nanoparticle technologies and the growth of vesicle-based drug delivery vectors provide exciting new opportunities for effective targeted drug delivery.

This Topical Collection explores these new frontiers in cancer diagnosis and treatment, and explores other emerging technologies which are disrupting traditional approaches used in the clinical management of cancer. 

Prof. Dr. Mary Bebawy
Prof. Dr. Michelle Hill
Collection Editors

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 short 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

  • extracellular vesicles
  • exosomes
  • microvesicles
  • apoptotic bodies
  • miRNA
  • liquid biopsy
  • drug delivery
  • diagnostics
  • nanotechnology
  • technology
  • liposome

Published Papers (9 papers)

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Research

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25 pages, 11184 KiB  
Article
Generation of Orthotopic Patient-Derived Xenografts in Humanized Mice for Evaluation of Emerging Targeted Therapies and Immunotherapy Combinations for Melanoma
by Chi Yan, Caroline A. Nebhan, Nabil Saleh, Rebecca Shattuck-Brandt, Sheau-Chiann Chen, Gregory D. Ayers, Vivian Weiss, Ann Richmond and Anna E. Vilgelm
Cancers 2023, 15(14), 3695; https://doi.org/10.3390/cancers15143695 - 20 Jul 2023
Cited by 3 | Viewed by 1571
Abstract
Current methodologies for developing PDX in humanized mice in preclinical trials with immune-based therapies are limited by GVHD. Here, we compared two approaches for establishing PDX tumors in humanized mice: (1) PDX are first established in immune-deficient mice; or (2) PDX are initially [...] Read more.
Current methodologies for developing PDX in humanized mice in preclinical trials with immune-based therapies are limited by GVHD. Here, we compared two approaches for establishing PDX tumors in humanized mice: (1) PDX are first established in immune-deficient mice; or (2) PDX are initially established in humanized mice; then established PDX are transplanted to a larger cohort of humanized mice for preclinical trials. With the first approach, there was rapid wasting of PDX-bearing humanized mice with high levels of activated T cells in the circulation and organs, indicating immune-mediated toxicity. In contrast, with the second approach, toxicity was less of an issue and long-term human melanoma tumor growth and maintenance of human chimerism was achieved. Preclinical trials from the second approach revealed that rigosertib, but not anti-PD-1, increased CD8/CD4 T cell ratios in spleen and blood and inhibited PDX tumor growth. Resistance to anti-PD-1 was associated with PDX tumors established from tumors with limited CD8+ T cell content. Our findings suggest that it is essential to carefully manage immune editing by first establishing PDX tumors in humanized mice before expanding PDX tumors into a larger cohort of humanized mice to evaluate therapy response. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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9 pages, 1373 KiB  
Communication
Delay of Aortic Arterial Input Function Time Improves Detection of Malignant Vertebral Body Lesions on Dynamic Contrast-Enhanced MRI Perfusion
by Felipe Camelo, Kyung K. Peck, Atin Saha, Julio Arevalo-Perez, John K. Lyo, Jamie Tisnado, Eric Lis, Sasan Karimi and Andrei I. Holodny
Cancers 2023, 15(8), 2353; https://doi.org/10.3390/cancers15082353 - 18 Apr 2023
Viewed by 868
Abstract
Dynamic contrast-enhanced MRI (DCE) is an emerging modality in the study of vertebral body malignancies. DCE-MRI analysis relies on a pharmacokinetic model, which assumes that contrast uptake is simultaneous in the feeding of arteries and tissues of interest. While true in the highly [...] Read more.
Dynamic contrast-enhanced MRI (DCE) is an emerging modality in the study of vertebral body malignancies. DCE-MRI analysis relies on a pharmacokinetic model, which assumes that contrast uptake is simultaneous in the feeding of arteries and tissues of interest. While true in the highly vascularized brain, the perfusion of the spine is delayed. This delay of contrast reaching vertebral body lesions can affect DCE-MRI analyses, leading to misdiagnosis for the presence of active malignancy in the bone marrow. To overcome the limitation of delayed contrast arrival to vertebral body lesions, we shifted the arterial input function (AIF) curve over a series of phases and recalculated the plasma volume values (Vp) for each phase shift. We hypothesized that shifting the AIF tracer curve would better reflect actual contrast perfusion, thereby improving the accuracy of Vp maps in metastases. We evaluated 18 biopsy-proven vertebral body metastases in which standard DCE-MRI analysis failed to demonstrate the expected increase in Vp. We manually delayed the AIF curve for multiple phases, defined as the scan-specific phase temporal resolution, and analyzed DCE-MRI parameters with the new AIF curves. All patients were found to require at least one phase-shift delay in the calculated AIF to better visualize metastatic spinal lesions and improve quantitation of Vp. Average normalized Vp values were 1.78 ± 1.88 for zero phase shifts (P0), 4.72 ± 4.31 for one phase shift (P1), and 5.59 ± 4.41 for two phase shifts (P2). Mann–Whitney U tests obtained p-values = 0.003 between P0 and P1, and 0.0004 between P0 and P2. This study demonstrates that image processing analysis for DCE-MRI in patients with spinal metastases requires a careful review of signal intensity curve, as well as a possible adjustment of the phase of aortic AIF to increase the accuracy of Vp. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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17 pages, 2746 KiB  
Article
A Simple 3D Cell Culture Method for Studying the Interactions between Human Mesenchymal Stromal/Stem Cells and Patients Derived Glioblastoma
by Lisa Oliver, Arturo Álvarez-Arenas, Céline Salaud, Juan Jiménez-Sanchez, Gabriel F. Calvo, Juan Belmonte-Beitia, Stephanie Blandin, Luciano Vidal, Victor Pérez, Dominique Heymann and François M. Vallette
Cancers 2023, 15(4), 1304; https://doi.org/10.3390/cancers15041304 - 18 Feb 2023
Cited by 1 | Viewed by 2056
Abstract
We have developed a 3D biosphere model using patient-derived cells (PDCs) from glioblastoma (GBM), the major form of primary brain tumors in adult, plus cancer-activated fibroblasts (CAFs), obtained by culturing mesenchymal stem cells with GBM conditioned media. The effect of MSC/CAFs on the [...] Read more.
We have developed a 3D biosphere model using patient-derived cells (PDCs) from glioblastoma (GBM), the major form of primary brain tumors in adult, plus cancer-activated fibroblasts (CAFs), obtained by culturing mesenchymal stem cells with GBM conditioned media. The effect of MSC/CAFs on the proliferation, cell-cell interactions, and response to treatment of PDCs was evaluated. Proliferation in the presence of CAFs was statistically lower but the spheroids formed within the 3D-biosphere were larger. A treatment for 5 days with Temozolomide (TMZ) and irradiation, the standard therapy for GBM, had a marked effect on cell number in monocultures compared to co-cultures and influenced cancer stem cells composition, similar to that observed in GBM patients. Mathematical analyses of spheroids growth and morphology confirm the similarity with GBM patients. We, thus, provide a simple and reproducible method to obtain 3D cultures from patient-derived biopsies and co-cultures with MSC with a near 100% success. This method provides the basis for relevant in vitro functional models for a better comprehension of the role of tumor microenvironment and, for precision and/or personalized medicine, potentially to predict the response to treatments for each GBM patient. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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10 pages, 1610 KiB  
Article
Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores—Assessment of the Binding Behavior to Cancer Cells
by Sarah Beyer, Martha Kimani, Yuecheng Zhang, Alejandra Verhassel, Louise Sternbæk, Tianyan Wang, Jenny L. Persson, Pirkko Härkönen, Emil Johansson, Remi Caraballo, Mikael Elofsson, Kornelia Gawlitza, Knut Rurack, Lars Ohlsson, Zahra El-Schich, Anette Gjörloff Wingren and Maria M. Stollenwerk
Cancers 2022, 14(8), 1875; https://doi.org/10.3390/cancers14081875 - 08 Apr 2022
Cited by 7 | Viewed by 2494
Abstract
Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell [...] Read more.
Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell surface expression of SA. However, these protein molecules are usually expensive and easily denatured, which calls for the development of alternative glycan-specific receptors and cell imaging technologies. In this study, SA-imprinted fluorescent core-shell molecularly imprinted polymer particles (SA-MIPs) were employed to recognize SA on the cell surface of cancer cell lines. The SA-MIPs improved suspensibility and scattering properties compared with previously used core-shell SA-MIPs. Although SA-imprinting was performed using SA without preference for the α2,3- and α2,6-SA forms, we screened the cancer cell lines analyzed using the lectins Maackia Amurensis Lectin I (MAL I, α2,3-SA) and Sambucus Nigra Lectin (SNA, α2,6-SA). Our results show that the selected cancer cell lines in this study presented a varied binding behavior with the SA-MIPs. The binding pattern of the lectins was also demonstrated. Moreover, two different pentavalent SA conjugates were used to inhibit the binding of the SA-MIPs to breast, skin, and lung cancer cell lines, demonstrating the specificity of the SA-MIPs in both flow cytometry and confocal fluorescence microscopy. We concluded that the synthesized SA-MIPs might be a powerful future tool in the diagnostic analysis of various cancer cells. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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15 pages, 5997 KiB  
Article
Cell-Main Spectra Profile Screening Technique in Simulation of Circulating Tumour Cells Using MALDI-TOF Mass Spectrometry
by Wararat Chiangjong, Sebastian Chakrit Bhakdi, Noppawan Woramongkolchai, Thitinee Vanichapol, Nutkridta Pongsakul, Suradej Hongeng and Somchai Chutipongtanate
Cancers 2021, 13(15), 3775; https://doi.org/10.3390/cancers13153775 - 27 Jul 2021
Cited by 1 | Viewed by 2326
Abstract
Circulating atypical cells (CAC) are released from a primary tumour site into peripheral blood and are indicators of cancer metastasis. CAC occur at very low frequency in circulating blood, and their detection remains challenging. Moreover, white blood cells (WBC) are the major contaminant [...] Read more.
Circulating atypical cells (CAC) are released from a primary tumour site into peripheral blood and are indicators of cancer metastasis. CAC occur at very low frequency in circulating blood, and their detection remains challenging. Moreover, white blood cells (WBC) are the major contaminant in enriched CAC samples. Here, we developed matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) as a novel CAC characterization platform. Main spectra profiles (MSP) of normal and cancer cells were generated by MALDI-TOF MS, and a cell-main spectra database was then compiled and analysed using the MALDI Biotyper software. Logarithmic scores accurately predicted distinct cell types. The feasibility of this workflow was then validated using simulated samples, which were prepared by 5000 WBC of three healthy individuals spiked with varying numbers (3, 6, 12, 25, 50, and 100) of lung, colon, or prostate cancer cells. MALDI-TOF MS was able to detect cancer cells down to six cells over the background noise of 5000 WBC with significantly higher predictive scores as compared to WBC alone. Further development of cell-MSP database to cover all cancer types sourced from cell lines and patient tumours may enable the use of MALDI-TOF MS as a cancer-screening platform in clinical settings in the future. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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18 pages, 3243 KiB  
Article
Development of EndoScreen Chip, a Microfluidic Pre-Endoscopy Triage Test for Esophageal Adenocarcinoma
by Julie A. Webster, Alain Wuethrich, Karthik B. Shanmugasundaram, Renee S. Richards, Wioleta M. Zelek, Alok K. Shah, Louisa G. Gordon, Bradley J. Kendall, Gunter Hartel, B. Paul Morgan, Matt Trau and Michelle M. Hill
Cancers 2021, 13(12), 2865; https://doi.org/10.3390/cancers13122865 - 08 Jun 2021
Cited by 4 | Viewed by 2848
Abstract
The current endoscopy and biopsy diagnosis of esophageal adenocarcinoma (EAC) and its premalignant condition Barrett’s esophagus (BE) is not cost-effective. To enable EAC screening and patient triaging for endoscopy, we developed a microfluidic lectin immunoassay, the EndoScreen Chip, which allows sensitive multiplex serum [...] Read more.
The current endoscopy and biopsy diagnosis of esophageal adenocarcinoma (EAC) and its premalignant condition Barrett’s esophagus (BE) is not cost-effective. To enable EAC screening and patient triaging for endoscopy, we developed a microfluidic lectin immunoassay, the EndoScreen Chip, which allows sensitive multiplex serum biomarker measurements. Here, we report the proof-of-concept deployment for the EAC biomarker Jacalin lectin binding complement C9 (JAC-C9), which we previously discovered and validated by mass spectrometry. A monoclonal C9 antibody (m26 3C9) was generated and validated in microplate ELISA, and then deployed for JAC-C9 measurement on EndoScreen Chip. Cohort evaluation (n = 46) confirmed the expected elevation of serum JAC-C9 in EAC, along with elevated total serum C9 level. Next, we asked if the small panel of serum biomarkers improves detection of EAC in this cohort when used in conjunction with patient risk factors (age, body mass index and heartburn history). Using logistic regression modeling, we found that serum C9 and JAC-C9 significantly improved EAC prediction from AUROC of 0.838 to 0.931, with JAC-C9 strongly predictive of EAC (vs. BE OR = 4.6, 95% CI: 1.6–15.6, p = 0.014; vs. Healthy OR = 4.1, 95% CI: 1.2–13.7, p = 0.024). This proof-of-concept study confirms the microfluidic EndoScreen Chip technology and supports the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy. Future work will expand the number of markers on EndoScreen Chip from our list of validated EAC biomarkers. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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Review

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17 pages, 11844 KiB  
Review
Pseudocontinuous Arterial Spin Labeling: Clinical Applications and Usefulness in Head and Neck Entities
by Fumine Tanaka, Maki Umino, Masayuki Maeda, Ryohei Nakayama, Katsuhiro Inoue, Ryota Kogue, Makoto Obara and Hajime Sakuma
Cancers 2022, 14(16), 3872; https://doi.org/10.3390/cancers14163872 - 11 Aug 2022
Cited by 5 | Viewed by 1782
Abstract
As functional magnetic resonance imaging, arterial spin labeling (ASL) techniques have been developed to provide quantitative tissue blood flow measurements, which can improve the performance of lesion diagnosis. ASL does not require contrast agents, thus, it can be applied to a variety of [...] Read more.
As functional magnetic resonance imaging, arterial spin labeling (ASL) techniques have been developed to provide quantitative tissue blood flow measurements, which can improve the performance of lesion diagnosis. ASL does not require contrast agents, thus, it can be applied to a variety of patients regardless of renal impairments and contrast agent allergic reactions. The clinical implementation of head and neck lesions is limited, although, in recent years, ASL has been increasingly utilized in brain lesions. Here, we review the development of the ASL techniques, including pseudocontinuous ASL (pCASL). We compare readout methods between three-dimensional (3D) turbo spin-echo and 2D echo planar pCASL for the clinical applications of pCASL to head and neck lesions. We demonstrate the clinical usefulness of 3D pCASL for diagnosing various entities, including inflammatory lesions, hypervascular lesions, and neoplasms; for evaluating squamous cell carcinoma (SCC) treatment responses, and for predicting SCC prognosis. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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17 pages, 1836 KiB  
Review
Elucidating the Role of Extracellular Vesicles in Pancreatic Cancer
by Akbar Lulu Marzan and Sarah Elizabeth Stewart
Cancers 2021, 13(22), 5669; https://doi.org/10.3390/cancers13225669 - 12 Nov 2021
Cited by 8 | Viewed by 2666
Abstract
Pancreatic cancer is one of the deadliest cancers worldwide, with a 5-year survival rate of less than 10%. This dismal survival rate can be attributed to several factors including insufficient diagnostics, rapid metastasis and chemoresistance. To identify new treatment options for improved patient [...] Read more.
Pancreatic cancer is one of the deadliest cancers worldwide, with a 5-year survival rate of less than 10%. This dismal survival rate can be attributed to several factors including insufficient diagnostics, rapid metastasis and chemoresistance. To identify new treatment options for improved patient outcomes, it is crucial to investigate the underlying mechanisms that contribute to pancreatic cancer progression. Accumulating evidence suggests that extracellular vesicles, including exosomes and microvesicles, are critical players in pancreatic cancer progression and chemoresistance. In addition, extracellular vesicles also have the potential to serve as promising biomarkers, therapeutic targets and drug delivery tools for the treatment of pancreatic cancer. In this review, we aim to summarise the current knowledge on the role of extracellular vesicles in pancreatic cancer progression, metastasis, immunity, metabolic dysfunction and chemoresistance, and discuss their potential roles as biomarkers for early diagnosis and drug delivery vehicles for treatment of pancreatic cancer. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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Other

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12 pages, 28280 KiB  
Systematic Review
The Evolving Role of Radiofrequency Guided Localisation in Breast Surgery: A Systematic Review
by Salim Tayeh, Umar Wazir and Kefah Mokbel
Cancers 2021, 13(19), 4996; https://doi.org/10.3390/cancers13194996 - 05 Oct 2021
Cited by 7 | Viewed by 2451
Abstract
Wire-guided localisation (WGL) has been the gold-standard for localising non-palpable breast lesions before excision. Due to its drawbacks, various wireless alternatives have been developed, including LOCalizer™, which is based on radio-frequency identification (RFID) technology. In this systematic review, we consulted EMBASE, Medline and [...] Read more.
Wire-guided localisation (WGL) has been the gold-standard for localising non-palpable breast lesions before excision. Due to its drawbacks, various wireless alternatives have been developed, including LOCalizer™, which is based on radio-frequency identification (RFID) technology. In this systematic review, we consulted EMBASE, Medline and PubMed databases using appropriate search terms regarding the use of RFID technology in the localisation of occult breast lesions. Retrospective and prospective studies were included if they quoted the number of patients, rate of successful placement, retrieval rate, margin positivity rate and the re-excision rate. In addition, studies comparing RFID to WGL were also included and analysed separately. Seven studies were included in this systematic review spanning 1151 patients and 1344 tags. The pooled deployment rate was 99.1% and retrieval rate was 100%. Re-excision rate was 13.9%. One complication was identified. Two studies compared RFID with WGL (128 vs. 282 patients respectively). For both techniques the re-excision rate was 15.6% (20/128 vs. 44/282 respectively, p value is 0.995). Based on our review, LOCalizer™ is safe and non-inferior to WGL in terms of successful localisation and re-excision rates. However, further research is required to assess the cost effectiveness of this approach and its impact on the aesthetic outcome compared with WGL and other wire free technologies to better inform decision making in service planning and provision. Full article
(This article belongs to the Special Issue Emerging Technologies in Cancer Diagnostics and Therapeutics)
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