Menu

Close

PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery

Nathalie Conte, Jeremy Mason, Csaba Halmagyi, Steven B Neuhauser, Abayomi Mosaku, Dale A Begley, Debra M Krupke, Helen Parkinson, Terrence Meehan, Carol J Bult

Preprint posted on April 05, 2018 https://www.biorxiv.org/content/early/2018/04/05/291443

An open information resource for patient-derived tumor models: PDX Finder as a searchable portal to improve visibility, transparency and communication in cutting-edge cancer research.

Selected by Carmen Adriaens

Background

In the past 15 years, tens of laboratories all over the world have implemented patient-derived tumor xenograft (PDX) models as a powerful tool to study cancer. The principle is simple: upon biopsy in the clinic, a piece or a suspension of the resected tumorous tissue is engrafted either orthotopically or subcutaneously in an immunocompromised mouse. If the graft is successful, the grown tumor can be re-transplanted (expanded) into another set of mice (2nd generation) and so on, until several mice bear the same parent tumor and can be used for experiments. Over generations of host mice, the human tumor stroma is usually replaced by mouse stroma, but the cancerous tissue retains its principal molecular and histological characteristics.

PDX models have several advantages over in vitro– or cell line graft- based techniques. For instance, they retain well the cellular heterogeneity found in the original tumors and they usually respond to a treatment in a manner similar to the donor. They can even be predictive of resistance development or response rate. Moreover, as opposed to genetically engineered mouse models (GEMMs), the cells are of human origin, and data generated for the models is directly relevant to the study of human cancer biology.

PDX models are used for several cancer-related applications. For instance, the engraftment rate and success of a tumor can be examined diagnostically to determine stage and aggressiveness. They are employed to resolve important biological questions such as what the tumor heterogeneity is, whether a cell-of-origin exists, or if certain tumor cells are intrinsically resistant to therapy. Recently, the field has imagined a more clinically relevant application: although expensive and not devoid of risk (and if anything, still in a very controversial light), PDX models could be used as “avatars” for cancer patients. In such a scenario, several drug combinations and treatment courses can be tested and characterized before an actual therapy scheme is established in the clinic.

 

The problem

 

Alone, we can do so little; together, we can do so much.” — Helen Keller

 

Although many labs have developed PDX models, the techniques to do so are not standardized and the reporting and availability of data, especially, are limited and scattered, or very heterogeneous among different groups. In a community effort, several world-wide consortia recently established PDX-MI, a Minimal Information set of guidelines that recommends PDX users to report “essential” and “desirable” data modules when new models or research is published (Meehan, Conte et al. Cancer Research, 2017). Since the use of PDX is rapidly expanding, there is a pressing need for a centralized database containing the available models and their minimal information. A such, they can be shared globally to prevent redundant studies and the perfect PDX and associated data can be easily found for the specific research question asked.

 

The preprint

In this preprint, Conte et al. present PDX Finder (www.PDXfinder.org), an online database aiming to solve the decentralization of available models and the information about them. For now, seven PDX centers (one in Italy, six in the US) have joined the database. The authors invite all other centers from around the world to participate.

PDX finder provides a searchable platform for PDX models of different cancer types, and searches can be narrowed to the geographical location of the model, the anatomical system, collection site, molecular characteristics, type of host and patient, mouse generation etc. It will be updated with clinically and biologically relevant information, where available, and aims to improve the visibility of cancer models for future studies.

 

My opinion

Overall, I think this preprint is a clear and concise description of the website and serves its citation and dissemination purposes well. Importantly, I believe this manuscript is a worthy attempt to address a recurrent issue in modern science: the lack of transparency, standardization, data availability, and mobility of reagents and skills.

This preprint and the PDX Finder website is a small but important step forward by aiming to centralize the information. It may help to increase the visibility of available models and stimulate communication between biologists, clinicians, and informaticians. Hopefully, the platform will encourage exchange among different centers and laboratories, which will be especially valuable when done within the framework of the PDX-MI. Furthermore, the use of animal models for research and clinical purpose is obviously not without controversy. This database may hence contribute to the three R’s – Replace, Reduce, Refine. A central platform can help to avoid duplicate models for fundamental research, and in contrast, may reveal gaps in molecular subtypes for individual tumor type PDX models.

In conclusion, I believe that, although as with all animal models their use needs reasonable caution, overall PDX models are an excellent and robust tool to study cancer. In past years they appear to have taken center stage successfully and seem ready to revolutionize cancer research. I like to think we all strive towards the same objective of understanding and trying to cure cancer, and we will need to bundle our efforts to succeed. Ultimately, PDX Finder may help to achieve that goal in an effective and transparent manner.

 

 

Tags: database, disease model, issues in science, patient derived tumor xenograft, worldwide consortia

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the cancer biology category:

    Also in the cell biology category:

    Rearing temperature and fatty acid supplementation jointly affect membrane fluidity and heat tolerance in Daphnia

    Dominik Martin-Creuzburg, Bret L. Coggins, Dieter Ebert, et al.



    Selected by Alexander Little

    Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction

    John K Eykelenboom, Marek Gierlinski, Zuojun Yue, et al.

    AND

    Quantitative imaging of chromatin decompaction in living cells

    Elisa Dultz, Roberta Mancini, Guido Polles, et al.



    Selected by Carmen Adriaens, Gautam Dey

    Optogenetic reconstitution reveals that Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura, Toyoaki Natsume, Masato T Kanemaki, et al.



    Selected by Arnaud Monnard

    1

    Optogenetic reconstitution reveals that Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura, Toyoaki Natsume, Masato T Kanemaki, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

    Pierre ROME, Hiroyuki OHKURA



    Selected by Binyam Mogessie

    ERM proteins: The missing actin linkers in clathrin-mediated endocytosis

    Audun Sverre Kvalvaag, Kay Oliver Schink, Andreas Brech, et al.



    Selected by Nicola Stevenson

    Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity

    Adan Horta, Kevin Monahan, Lisa Bashkirova, et al.



    Selected by Boyan Bonev

    A non-canonical role for dynamin-1 in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells

    Saipraveen Srinivasan, Christoph J. Burckhardt, Madhura Bhave, et al.



    Selected by Penelope La-Borde

    Atomic model of microtubule-bound tau

    Elizabeth H Kellogg, Nisreen M.A. Hejab, Simon Poepsel, et al.



    Selected by Satish Bodakuntla

    1

    Spatial Self-Organization Resolves Conflicts Between Individuality and Collective Migration

    Xiongfei Fu, Setsu Kato, Junjiajia Long, et al.



    Selected by Amanda Haage

    1

    PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery

    Nathalie Conte, Jeremy Mason, Csaba Halmagyi, et al.



    Selected by Carmen Adriaens

    Two contractile pools of actomyosin distinctly load and tune E-cadherin levels during morphogenesis

    Girish R. Kale, Xingbo Yang, Jean-Marc Philippe, et al.



    Selected by Arnaud Monnard

    HIF1-alpha expressing cells induce a hypoxic-like response in neighbouring cancer cells

    Hannah Harrison, Henry J Pegg, Jamie Thompson, et al.



    Selected by Anh Hoang Le

    Higher-Order Organization Principles of Pre-translational mRNPs

    Mihir Metkar, Hakan Ozadam, Bryan R. Lajoie, et al.



    Selected by Carmen Adriaens

    Capturing the onset of PRC2-mediated repressive domain formation

    Ozgur Oksuz, Varun Narendra, Chul-Hwan Lee, et al.



    Selected by Boyan Bonev

    RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs

    Mark A McClintock, Carly I Dix, Christopher M Johnson, et al.

    AND

    Recruitment of Two Dyneins to an mRNA-Dependent Bicaudal D Transport Complex

    Thomas E. Sladewski, Neil Billington, M. Yusuf Ali, et al.



    Selected by Dmitry Nashchekin

    Also in the genetics category:

    Cancer modeling by Transgene Electroporation in Adult Zebrafish (TEAZ)

    Scott J Callahan, Stephanie Tepan, Yan M Zhang, et al.



    Selected by Hannah Brunsdon

    Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin

    Jacob Daane, Jennifer Lanni, Ina Rothenberg, et al.



    Selected by Alberto Rosello-Diez

    1

    Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of cell division, differentiation, and loss

    Judy Martin, Erin Nicole Sanders, Paola Moreno-Roman, et al.



    Selected by Natalie Dye

    F-actin patches nucleated on chromosomes coordinate capture by microtubules in oocyte meiosis

    Mariia Burdyniuk, Andrea Callegari, Masashi Mori, et al.



    Selected by Binyam Mogessie

    Comprehensive characterization of transcript diversity at the human NODAL locus

    Scott D Findlay, Lynne-Marie Postovit



    Selected by Christian Ramos

    Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth

    Alberto Rosello-Diez, Linda Madisen, Sebastien Bastide, et al.



    Selected by Natalie Dye

    Precise temporal regulation of alternative splicing during neural development

    Sebastien M Weyn-Vanhentenryck, Huijuan Feng, Dmytro Ustianenko, et al.



    Selected by James Gagnon

    Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling

    Claudio Cantù, Anastasia Felker, Dario Zimmerli, et al.



    Selected by Andreas van Impel

    Insect wings and body wall evolved from ancient leg segments

    Heather S Bruce, Nipam H Patel

    AND

    Two sets of wing homologs in the crustacean, Parhyale hawaiensis

    Courtney M Clark-Hachtel, Yoshinori Tomoyasu



    Selected by Erik Clark

    2

    Also in the genomics category:

    Close

    We want to make our website, and the services we provide, useful and reliable. This sometimes involves placing small amounts of information called cookies on the device you used to access the internet. If you continue to use this website we will assume you are happy to accept our cookies.

    Accept