PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery
Preprint posted on April 05, 2018 https://www.biorxiv.org/content/early/2018/04/05/291443
Article now published in Nucleic Acids Research at http://dx.doi.org/10.1093/nar/gky984
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 AdriaensCategories: cancer biology, cell biology, clinical trials, genetics, genomics
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.
Posted on: 20th April 2018
Read preprintSign up to customise the site to your preferences and to receive alerts
Register hereAlso in the cancer biology category:
EccDNA formation is dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA double-strand break
Selected by | Ram |
1
ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination deficient cells
Selected by | Giuseppina D'Alessandro |
1
Endothelial cell invasiveness is controlled by myosin IIA-dependent inhibition of Arp2/3 activity
Selected by | Mariana De Niz |
1
Also in the cell biology category:
Also in the clinical trials category:
Bromodomain Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV2 Infection in Pre-Clinical Models
Selected by | Alexander Ward, Osvaldo Contreras |
1
Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis
Selected by | Kristina Kuhbandner |
1
A Transcriptional Switch Governing Fibroblast Plasticity Underlies Reversibility of Chronic Heart Disease
Selected by | Osvaldo Contreras, Alexander Ward |
Also in the genetics category:
Also in the genomics category:
Dissecting Mammalian Spermatogenesis Using Spatial Transcriptomics
Selected by | Martin Estermann |
EccDNA formation is dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA double-strand break
Selected by | Ram |
1
Association analysis of repetitive elements and R-loop formation across species
Selected by | Ram |
1
preListscancer biology category:
in theSingle Cell Biology 2020
A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.
List by | Alex Eve |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
List by | Madhuja Samaddar, Ramona Jühlen, Amanda Haage, Laura McCormick, Maiko Kitaoka |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
List by | Rob Hynds |
Anticancer agents: Discovery and clinical use
Preprints that describe the discovery of anticancer agents and their clinical use. Includes both small molecules and macromolecules like biologics.
List by | Zhang-He Goh |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
List by | Joseph Jose Thottacherry |
Also in the cell biology category:
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka, Madhuja Samaddar, Miguel V. Almeida, Sejal Davla, Jennifer Ann Black, Dey Lab |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Preprint missing? Don't hesitate to let us know.
List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
List by | Madhuja Samaddar, Ramona Jühlen, Amanda Haage, Laura McCormick, Maiko Kitaoka |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
List by | Dey Lab |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
List by | Sandra Franco Iborra |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
List by | Dey Lab, Amanda Haage |
Also in the clinical trials category:
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
List by | Sandra Malmgren Hill |
Antimicrobials: Discovery, clinical use, and development of resistance
Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.
List by | Zhang-He Goh |
Also in the genetics category:
EMBL Conference: From functional genomics to systems biology
Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020
List by | Jesus Victorino |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka, Madhuja Samaddar, Miguel V. Almeida, Sejal Davla, Jennifer Ann Black, Dey Lab |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
List by | Sandra Malmgren Hill |
Zebrafish immunology
A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.
List by | Shikha Nayar |
Also in the genomics category:
EMBL Conference: From functional genomics to systems biology
Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020
List by | Jesus Victorino |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka, Madhuja Samaddar, Miguel V. Almeida, Sejal Davla, Jennifer Ann Black, Dey Lab |