Cancer Research Technology Research Articles

Emerging Technologies for Cancer Research: Towards Personalized Medicine with Microfluidic Platforms and 3D Tumor Models.

In the present review, we describe three hot topics in cancer research such as circu-lating tumor cells, exosomes, and 3D environment models. The first section is dedicated to microfluidic platforms for detecting circulating tumor cells, including both affinity-based methods that take advantage of antibodies and aptamers, and “label-free” approaches, ex-ploiting cancer cells physical features and, more recently, abnormal cancer metabolism. In the second section, we briefly describe the biology of exosomes and their role in cancer, as well as conventional techniques for their isolation and innovative microfluidic platforms. In the third section, the importance of tumor microenvironment is highlighted, along with techniques for modeling it in vitro. Finally, we discuss limitations of two-dimensional mono-layer methods and describe advantages and disadvantages of different three-dimensional tumor systems for cell-cell interaction analysis and their potential applications in cancer management.

Emerging technologies and innovation policies in India: how disparities in cancer research might be furthering health inequities?

ABSTRACT Inequity in health research is understood as a major impediment to development.The paper uses empirical analysis performed on a unique data set of publications and clinical trials related to cancer research to explore the public policy dimensions of health care research in India. It traces disparities that result from predilections in science technology and innovation policies in India. The paper analyses disparity in health research using emerging technologies and its implications for equity in health research. The paper argues that the use of emerging technologies in cancer research has shifted research focus from cancers affecting poor population in India. Abbreviations AA – Age Adjusted Incidence Rates; CTRI – Clinical Trail Registry of India; DBT – Department of Biotechnology; DST – Department of Science and Technology; ICMR – Indian Council for Medical Research; Mabs – Monoclonal antibodies; NBDS – National Biotechnology Development Strategy; NCI – National Cancer Institute; NSTI – Nanoscience and Technology Initiative; SCI – Science Citation Index; TB – Tuberculosis; WOS – Web of Science.

Application of omic technologies in cancer research

Understanding the biology of health and diseases such as cancer, generating insight into the triggers and potentiators of disease and the development of therapeutic approaches to counter and treat disease requires detailed interrogation of inherited genes, and the dynamic positioning of the transcriptome and proteome. In the last 10 years, significant technological developments and increases in sample throughput capabilities have led to a dramatic increase in the size and complexity of the datasets that can be generated. A key challenge now is to develop robust approaches for analysing and interpreting these, and converting data into biologically- and clinically-relevant information. Herein, we provide an overview of approaches for acquiring, integrating and interpreting complex datasets generated using multiple omic platforms, with a focus on the field of cancer research, and highlight key successful data handling and integration applications.

In vivo optical imaging of cancer cell function and tumor microenvironment.

In vivo optical imaging using fluorescence and bioluminescence is superior to other methods in terms of spatiotemporal resolution and specificity, and represents a new technology for comprehensively studying living organisms in a less invasive way. Nowadays, it is an indispensable technology for studying many aspects of cancer biology, including dynamic invasion and metastasis. In observations of fluorescence or bioluminescence signals in a living body, various problems were caused by optical characteristics such as absorption and scattering and, therefore, observation of deep tissue was difficult. Recent developments in techniques for observation of the deep tissues of living animals overcame this difficulty by improving bioluminescent proteins, fluorescent proteins, and fluorescent dyes, as well as detection technologies such as two‐photon excitation microscopy. In the present review, we introduce these technological developments and in vivo application of bioluminescence and fluorescence imaging, and discuss future perspectives on the use of in vivo optical imaging technology in cancer research.

Abstract 2589: Identifying cancer susceptibility variants and genes using whole exome and genome sequencing: a literature review

Abstract The application of Next Generation Sequencing (NGS) technologies in cancer research enabled the discovery of novel somatic mutations at an unprecedented speed through efficient high-throughput profiling of DNA variation in tumor samples. In contrast, the identification through NGS studies of germline variation associated with cancer has been more difficult and with limited consensus around best practices for study design and analytical techniques. We performed a review of the 2005-2016 PubMed English literature for genome-wide germline sequencing studies that were aimed at identifying new cancer susceptibility genes or variants. We extracted and summarized the experimental and analytical designs, methods and tools implemented in the selected literature together with their degree of success and limitations in identifying cancer susceptibility variants. About 80 in-scope publications were identified and examined in depth. The most studied cancer types were colorectal, breast, blood and lung and were investigated predominantly via whole exome sequencing (primarily using Illumina HiSeq) in familial cases of Caucasian ethnicity. Only 10 studies used whole genome sequencing and 15 adopted a case control study design. A large fraction of the familial studies was limited to 1 or 2 families and sequenced 2 or less cases per family. Reporting of key data quality information (e.g., human sequence coverage) was inconsistent throughout the publications. While the methods for sequence alignment and variant calling converged towards those implemented in established bioinformatic tools (e.g., BWA, GATK), there were no standard approaches for filtering or prioritizing of variants. Most studies included some degree of technical validation, often restricted to the top few variants or genes. About 60% of the studies included replication in an independent group of cancer patients and 55% functionally validated their findings to some extent. Our work provides valuable data and insights to inform future sequencing studies of cancer genetic susceptibility, and points to the need for improving standardization and completeness in reporting of quality control metrics, study design rationale and interpretation of findings. Citation Format: Melissa Rotunno, Mindy Clyne, Tram Lam, Leah Mechanic, Danielle Daee, Stefanie Nelson, Elizabeth Gillanders, Alisa Goldstein. Identifying cancer susceptibility variants and genes using whole exome and genome sequencing: a literature review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2589. doi:10.1158/1538-7445.AM2017-2589

Advanced biomaterials and microengineering technologies to recapitulate the stepwise process of cancer metastasis.

Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic invitro models with physiologically relevant (i.e. invivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions.

CRISPR/Cas9: Transcending the Reality of Genome Editing.

With the expansion of the microbiology field of research, a new genome editing tool arises from the biology of bacteria that holds the promise of achieving precise modifications in the genome with a simplicity and versatility that surpasses previous genome editing methods. This new technique, commonly named CRISPR/Cas9, led to a rapid expansion of the biomedical field; more specifically, cancer characterization and modeling have benefitted greatly from the genome editing capabilities of CRISPR/Cas9. In this paper, we briefly summarize recent improvements in CRISPR/Cas9 design meant to overcome the limitations that have arisen from the nuclease activity of Cas9 and the influence of this technology in cancer research. In addition, we present challenges that might impede the clinical applicability of CRISPR/Cas9 for cancer therapy and highlight future directions for designing CRISPR/Cas9 delivery systems that might prove useful for cancer therapeutics.

Mass Spectrometry Imaging for the Investigation of Intratumor Heterogeneity.

One of the big clinical challenges in the treatment of cancer is the different behavior of cancer patients under guideline therapy. An important determinant for this phenomenon has been identified as inter- and intratumor heterogeneity. While intertumor heterogeneity refers to the differences in cancer characteristics between patients, intratumor heterogeneity refers to the clonal and nongenetic molecular diversity within a patient. The deciphering of intratumor heterogeneity is recognized as key to the development of novel therapeutics or treatment regimens. The investigation of intratumor heterogeneity is challenging since it requires an untargeted molecular analysis technique that accounts for the spatial and temporal dynamics of the tumor. So far, next-generation sequencing has contributed most to the understanding of clonal evolution within a cancer patient. However, it falls short in accounting for the spatial dimension. Mass spectrometry imaging (MSI) is a powerful tool for the untargeted but spatially resolved molecular analysis of biological tissues such as solid tumors. As it provides multidimensional datasets by the parallel acquisition of hundreds of mass channels, multivariate data analysis methods can be applied for the automated annotation of tissues. Moreover, it integrates the histology of the sample, which enables studying the molecular information in a histopathological context. This chapter will illustrate how MSI in combination with statistical methods and histology has been used for the description and discovery of intratumor heterogeneity in different cancers. This will give evidence that MSI constitutes a unique tool for the investigation of intratumor heterogeneity, and could hence become a key technology in cancer research.

A bioinformatics approach for precision medicine off-label drug drug selection among triple negative breast cancer patients.

Cancer has been extensively characterized on the basis of genomics. The integration of genetic information about cancers with data on how the cancers respond to target based therapy to help to optimum cancer treatment. The increasing usage of sequencing technology in cancer research and clinical practice has enormously advanced our understanding of cancer mechanisms. The cancer precision medicine is becoming a reality. Although off-label drug usage is a common practice in treating cancer, it suffers from the lack of knowledge base for proper cancer drug selections. This eminent need has become even more apparent considering the upcoming genomics data. In this paper, a personalized medicine knowledge base is constructed by integrating various cancer drugs, drug-target database, and knowledge sources for the proper cancer drugs and their target selections. Based on the knowledge base, a bioinformatics approach for cancer drugs selection in precision medicine is developed. It integrates personal molecular profile data, including copy number variation, mutation, and gene expression. By analyzing the 85 triple negative breast cancer (TNBC) patient data in the Cancer Genome Altar, we have shown that 71.7% of the TNBC patients have FDA approved drug targets, and 51.7% of the patients have more than one drug target. Sixty-five drug targets are identified as TNBC treatment targets and 85 candidate drugs are recommended. Many existing TNBC candidate targets, such as Poly (ADP-Ribose) Polymerase 1 (PARP1), Cell division protein kinase 6 (CDK6), epidermal growth factor receptor, etc., were identified. On the other hand, we found some additional targets that are not yet fully investigated in the TNBC, such as Gamma-Glutamyl Hydrolase (GGH), Thymidylate Synthetase (TYMS), Protein Tyrosine Kinase 6 (PTK6), Topoisomerase (DNA) I, Mitochondrial (TOP1MT), Smoothened, Frizzled Class Receptor (SMO), etc. Our additional analysis of target and drug selection strategy is also fully supported by the drug screening data on TNBC cell lines in the Cancer Cell Line Encyclopedia. The proposed bioinformatics approach lays a foundation for cancer precision medicine. It supplies much needed knowledge base for the off-label cancer drug usage in clinics.

Abstract A35: Innovative technologies for cancer research – NCI Strategy for supporting next generation of tools needed against cancer

Abstract The development of highly innovative technologies continues to be a high priority for accelerating or challenging existing basic and clinical cancer research paradigms. Epigenetic regulation and chromatin structural biology have offered compelling new opportunities for cancer researchers, but existing tools for investigating this biology are insufficient and new technology development research is needed. The National Institutes of Health (NIH) is the principle biomedical research funding agency of the US federal government, and recognizes that it is often difficult to achieve support for such research through existing program structures. The National Cancer Institute (NCI) is the largest institute of the NIH, and has established the Center for Strategic Scientific Initiatives (CSSI) to pioneer unique scientific and technology initiatives that help keep the NCI ahead of the scientific curve with respect to new and exciting cancer research areas and discoveries. This has involved the development and application of advanced technologies (e.g., Clinical Proteomic Technologies Against Cancer initiative), synergy of large-scale and investigator-initiated research (e.g., NCI Physical Sciences Oncology Network and Alliance for Cancer Nanotechnology), and/or forging novel partnerships that emphasize innovation, trans-disciplinary teams and convergence of scientific disciplines (e.g., The Cancer Genome Atlas) to enable the translation of discoveries into new interventions, both domestically and internationally, to detect, prevent and treat cancer more effectively. The longest standing program from CSSI is specifically tailored to address the need for highly innovative technology development necessary for advancing cancer research, and it is called the Innovative Molecular Analysis Technologies (IMAT) program. This program employs unique solicitation and review mechanisms better suited to appreciating the longer term potential of transformative technologies and designed to be more tolerant of the substantial risks often associated with such research. Research funding opportunities through this program were recently reissued, with a larger set-aside budget to grant up to 120 new awards through 2017. The unique aspects of both the solicitation and review of applications to this program will be presented, and several recently-supported research projects relevant to chromatin and epigenetics research will be highlighted to demonstrate the variety and high level of innovation evident in the IMAT portfolio of supported research. Potential projects of interest and identified technology gaps will also be discussed. Citation Format: Tony Dickherber. Innovative technologies for cancer research – NCI Strategy for supporting next generation of tools needed against cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A35.

The application of CRISPR/Cas9 genome editing technology in cancer research

The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease) genome editing technology has become more and more popular in gene editing because of its simple design and easy operation. Using the CRISPR/Cas9 system, researchers can perform site-directed genome modification at the base level. Moreover, it has been widely used in genome editing in multiple species and related cancer research. In this review, we summarize the application of the CRISPR/Cas9 system in cancer research based on the latest research progresses as well as our understanding of cancer research and genome editing techniques.

Transition at Technology in Cancer Research & Treatment

Transition at <i>Technology in Cancer Research &amp; Treatment</i>

Applications of iPSCs in Cancer Research.

Induced pluripotent stem cells (iPSCs) derived from reprogrammed somatic cells are emerging as one of the most versatile tools in biomedical research and pharmacological studies. Oncogenic transformation and somatic cell reprogramming are multistep processes that share some common features, and iPSCs generated from cancerous cells can help us better understand the molecular mechanisms underlying the initiation and progression of human cancers and overcome them. Aside from the mechanistic modeling of human tumorigenesis, immediate applications of this technology in cancer research include high-throughput drug screening, toxicological testing, early biomarker identification, and bioengineering of replacement tissues. Here, we review the current advances in generating iPSCs from cancer cell lines and patient-derived primary cancer tissues, and discuss their potential applications.

Keith Blundy.

The non-profit Cancer Research UK (CRUK) funds over £300 million worth of cancer research each year and, with the help of its development and commercialization arm Cancer Research Technology (CRT), has moved more than 30 partnered agents into preclinical and clinical development. Having established a small-molecule track record, CRUK now needs to build up more biologic know-how, says CRT Chief Executive Officer Keith Blundy. To this end, CRUK and AstraZeneca's antibody subsidiary, MedImmune, agreed in September to launch the joint CRUK-MEDI Alliance Laboratory. This fully collaborative and integrated partnership is a first of its kind, Blundy tells Asher Mullard.

Abstract 4679: Novel pathway mutations in malignant mesothelioma revealed by high-throughput DNA and RNA sequencing

Abstract Background: Malignant mesothelioma (MM) is an aggressive neoplasm associated with asbestos exposure. Because MM is usually diagnosed at an advanced stage and is largely unresponsive to conventional therapy, it is necessary to identify the signal pathways driving MM and to develop therapeutics specifically targeting these pathways. Materials and Methods: We carried out RNA sequencing of 12 MM cell lines and 4 clinical samples and exome sequencing of 6 MM cells using a so-called next-generation sequencer. We further performed pathway-targeted genome sequencing of 23 paired samples of MM tumor and normal tissue. Results: We identified 15 novel fusion genes by RNA sequencing and confirmed them by conventional Sanger sequencing and FISH analyses. We showed that the novel gene was included in both LOH and a fusion gene, and the gene which was critical tumor-suppressor roles caused two hit and was down-regulated. The gene has been identified as a central player of the emerging signaling pathway. We further identified the accumulation of mutations in 35% of the MMs by pathway-targeted genome sequencing. Conclusions: We indicated the need for the discovering molecular targets in the novel pathway in MMs. Our findings provide novel insights into the pathogenesis of MM and unequivocally demonstrate the power of sequencing technologies in cancer research. Citation Format: Akihiko Miyanaga, Mari Masuda, Koji Tsuta, Yuka Nakamura, Hisao Asamura, Akihiko Gemma, Tesshi Yamada. Novel pathway mutations in malignant mesothelioma revealed by high-throughput DNA and RNA sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4679. doi:10.1158/1538-7445.AM2014-4679

Abstract 3499: Funding innovative technologies for cancer research at the National Cancer Institute

Abstract In the fall of 2013, the National Cancer Institute re-launched the Innovative Molecular Analysis Technologies (IMAT) program, committing up to $10.5 million through unique funding mechanisms (3 year R21s and R33s) to better support investigators through both the early and advanced stages of technology development over traditional funding mechanisms for exploratory research. The IMAT program has supported the development of various analytical and sample processing platforms that have made substantial contributions across the cancer research continuum, and the process of winning an award remains highly competitive. A variety of IMAT-supported research projects will be highlighted to demonstrate the variety and high level of innovation evident in the IMAT portfolio of supported research. An emphasis will be placed on recently completed projects so that investigators interested in next generation tools may become aware of possible developments through NCI-funded projects for their research. In addition, trends from recently awarded projects will be described to provide insight for potential applicants on the nature of the program and the competition. Potential projects of interest and identified technology gaps will also be discussed. The IMAT program continues to represent a unique resource for highly innovative technology development. Citation Format: Anthony Dickherber. Funding innovative technologies for cancer research at the National Cancer Institute. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3499. doi:10.1158/1538-7445.AM2014-3499

Sequencing approaches in cancer treatment.

Use of sequencing approaches is an important aspect in the field of cancer genomics, where next-generation sequencing has already been utilized for targeting oncogenes or tumour-suppressor genes, that can be sequenced in a short time period. Alterations such as point mutations, insertions/deletions, copy number alterations, chromosomal rearrangements and epigenetic changes are encountered in cancer cell genomes, and application of various NGS technologies in cancer research will encounter such modifications. Rapid advancement in technology has led to exponential growth in the field of genomic analysis. The $1000 Genome Project (in which the goal is to sequence an entire human genome for $1000), and deep sequencing techniques (which have greater accuracy and provide a more complete analysis of the genome), are examples of rapid advancements in the field of cancer genomics. In this mini review, we explore sequencing techniques, correlating their importance in cancer therapy and treatment.

Magnetic resonance spectroscopy and beyond for pediatric brain tumors.

CNS OncologyVol. 3, No. 3 News & ViewsAsk the Experts: Magnetic resonance spectroscopy and beyond for pediatric brain tumorsAndrew C PeetAndrew C PeetSearch for more papers by this authorPublished Online:17 Jun 2014https://doi.org/10.2217/cns.14.12AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleReferences1 Gill SK, Wilson M, Davies NP et al. Diagnosing relapse in children's brain tumors using metabolite profiles. Neuro Oncol. 16, 156–164 (2014).Crossref, Medline, CAS, Google Scholar2 Wilson M, Cummins CL, MacPherson L et al. Magnetic resonance spectroscopy metabolite profiles predict survival in paediatric brain tumours. Eur. J. Cancer 49(2), 457–464 (2013).Crossref, Medline, CAS, Google Scholar3 Peet AC, Arvanitis TN, Leach MO, Waldman AD . . Functional imaging in adult and paediatric brain tumours. Nat. Rev. Clin. Oncol. 9, 706–711 (2012).Crossref, Google Scholar4 Vicente J, Fuster-Garcia E, Tortajad S et al. Accurate classification of childhood brain tumours by in vivo1H MRS – a multi-centre study. Eur. J. Cancer 49(3), 658–667 (2013). Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited ByIn vivo derivative NMR spectroscopy for simultaneous improvements of resolution and signal-to-noise-ratio: Case study, Glioma19 August 2021 | Journal of Mathematical Chemistry, Vol. 59, No. 9A Preliminary Study on the Diagnostic Efficacy of Proton Magnetic Resonance Spectroscopy at 3.0T in Rabbit With VX2 Liver Tumor10 August 2021 | Technology in Cancer Research & Treatment, Vol. 20Biological material collection to advance translational research and treatment of children with CNS tumours: position paper from the SIOPE Brain Tumour GroupThe Lancet Oncology, Vol. 19, No. 8 Vol. 3, No. 3 Follow us on social media for the latest updates Metrics Downloaded 48 times History Published online 17 June 2014 Published in print May 2014 Information© Future Medicine LtdDisclaimerThe opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Future Medicine Ltd.Financial & competing interests disclosureA Peet would like to acknowledge funding from an NIHR Research Professorship 13-0053. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download

Proteomic analysis of phosphorylation in cancer

Constitutive activity of kinases is known to be crucial for a tumor to maintain its malignant phenotype, a phenomenon which is often referred to as oncogene addiction. The in-depth analysis of aberrant signaling pathways by the analysis of protein phosphorylation has become feasible through recent advances in proteomics technology. In this article we will review developments in the field of phosphoproteomics and its application in cancer research. The most widely used technologies for the generic enrichment of phosphopeptides are discussed as well as targeted approaches for the analysis of a specific subset of phosphopeptides. Validation experiments of phosphorylation sites using targeted mass spectrometry are also explained. Finally, we will highlight applications of phosphoproteomic technology in cancer research using cell lines and tissue.

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