<img height="1" width="1" src="https://www.facebook.com/tr?id=1582471781774081&amp;ev=PageView &amp;noscript=1">
  • Menu
  • crown-logo-symbol-1-400x551

Find it Quickly

Get Started

Select the option that best describes what you are looking for

  • Services
  • Models
  • Scientific Information

Search Here For Services

Click Here to Start Over

Search Here For Models

Click Here to Start Over

Search Here For Scientific Information

Click Here to Start Over

In Vitro

Boost oncology drug discovery with XenoBase®, featuring the largest cell line selection and exclusive 3D organoid models. Benefit from OrganoidXplore™ and OmniScreen™ for rapid, in-depth analysis.

Learn More

In Vivo

Enhance drug development with our validated in vivo models, in vitro/ex vivo assays, and in silico modeling. Tailored solutions to optimize your candidates.

Learn More

Tissue

Experience ISO-certified biobanking quality. Access top biospecimens from a global clinical network, annotated by experts for precise research.

Learn More

Biomarkers and Bioanalysis

Leverage our global labs and 150+ scientists for fast, tailored project execution. Benefit from our expertise, cutting-edge tech, and validated workflows for reliable data outcomes.

Learn More

Data Science and Bioinformatics

Harness your data and discover biomarkers with our top bioinformatics expertise. Maximize data value and gain critical insights to accelerate drug discovery and elevate projects.

Learn More

KRAS

Accelerate innovative cancer treatments with our advanced models and precise drug screening for KRAS mutations, efficiently turning insights into clinical breakthroughs.

Learn More

EGFR

Advance translational pharmacology with our diverse pre-clinical models, robust assays, and data science-driven biomarker analysis, multi-omics, and spatial biology.

Learn More

Drug Resistance

Our suite integrates preclinical solutions, bioanalytical read-outs, and multi-omics to uncover drug resistance markers and expedite discovery with our unique four-step strategy.

Learn More

Patient Tissue

Enhance treatments with our human tumor and mouse models, including xenografts and organoids, for accurate cancer biology representation.

Learn More

Target to Lead Selection for ADCs and Biologics

Journey through the drug discovery pipeline from target discovery to in vivo pharmacology. Take advantage of the Largest biobank of patient-derived models, Model development capabilities, Cell-based assays for Screening ADCs, and advanced downstream analysis.

Learn More

Bioinformatics

Apply the most appropriate in silico framework to your pharmacology data or historical datasets to elevate your study design and analysis, and to improve your chances of clinical success.

Learn More

Biomarker Analysis

Integrate advanced statistics into your drug development projects to gain significant biological insight into your therapeutic candidate, with our expert team of bioinformaticians.

Learn More

CRISPR/Cas9

Accelerate your discoveries with our reliable CRISPR solutions. Our global CRISPR licenses cover an integrated drug discovery platform for in vitro and in vivo efficacy studies.

Learn More

Genomics

Rely on our experienced genomics services to deliver high quality, interpretable results using highly sensitive PCR-based, real-time PCR, and NGS technologies and advanced data analytics.

Learn More

In Vitro High Content Imaging

Gain more insights into tumor growth and disease progression by leveraging our 2D and 3D fluorescence optical imaging.

Learn More

Mass Spectrometry-based Proteomics

Next-generation ion mobility mass spectrometry (MS)-based proteomics services available globally to help meet your study needs.

Learn More

Ex Vivo Patient Tissue

Gain better insight into the phenotypic response of your therapeutic candidate in organoids and ex vivo patient tissue.

Learn More

Spatial Multi-Omics Analysis

Certified CRO services with NanoString GeoMx Digital Spatial Profiling.

Learn More

Biomarker Discovery

De-risk your drug development with early identification of candidate biomarkers and utilize our biomarker discovery services to optimize clinical trial design.

Learn More

DMPK Services

Rapidly evaluate your molecule’s pharmaceutical and safety properties with our in vivo drug metabolism and pharmacokinetic (DMPK) services to select the most robust drug formulations.

Learn More

Efficacy Testing

Explore how the novel HuGEMM™ and HuCELL™ platforms can assess the efficacy of your molecule and accelerate your immuno-oncology drug discovery programs.

Learn More

Laboratory Services

Employ cutting-edge multi-omics methods to obtain accurate and comprehensive data for optimal data-based decisions.

Learn More

Pharmacology & Bioanalytical Services

Leverage our suite of structural biology services including, recombinant protein expression and protein crystallography, and target validation services including RNAi.

Learn More

Screens

Find the most appropriate screen to accelerate your drug development: discover in vivo screens with MuScreen™ and in vitro cell line screening with OmniScreen™.

Learn More

Toxicology

Carry out safety pharmacology studies as standalone assessments or embedded within our overall toxicological profiling to assess cardiovascular, metabolic and renal/urinary systems.

Learn More

Preclinical Consulting Services

Learn more about how our consulting services can help to support your journey to the clinic.

Learn More

Our Company

Global CRO in California, USA offering preclinical and translational oncology platforms with high-quality in vivo, in vitro, and ex vivo models.

Learn More

Our Purpose

Learn more about the impact we make through our scientific talent, high-quality standards, and innovation.

Learn More

Our Responsibility

We build a sustainable future by supporting employee growth, fostering leadership, and exceeding customer needs. Our values focus on innovation, social responsibility, and community well-being.

Learn More

Meet Our Leadership Team

We build a sustainable future by fostering leadership, employee growth, and exceeding customer needs with innovation and social responsibility.

Learn More

Scientific Advisory Board

Our Scientific Advisory Board of experts shapes our strategy and ensures top scientific standards in research and development.

Learn More

News & Events

Stay updated with Crown Bioscience's latest news, achievements, and announcements. Check our schedule for upcoming events and plan your visit.

Learn More

Career Opportunities

Join us for a fast-paced career addressing life science needs with innovative technologies. Thrive in a respectful, growth-focused environment.

Learn More

Scientific Publications

Access our latest scientific research and peer-reviewed articles. Discover cutting-edge findings and insights driving innovation and excellence in bioscience.

Learn More

Resources

Discover valuable insights and curated materials to support your R&D efforts. Explore the latest trends, innovations, and expertly curated content in bioscience.

Learn More

Blogs

Explore our blogs for the latest insights, research breakthroughs, and industry trends. Stay educated with expert perspectives and in-depth articles driving innovation in bioscience.

Learn More

  • Platforms
  • Target Solutions
  • Technologies
  • Service Types

The Benefits of PDX Models in Head and Neck Cancer Research

the benefits of patient-derived xenografts (PDX) in head and neck cancer researchExplore why patient-derived xenografts (PDX) are an important model in head and neck cancer research, particularly for studying radiation response and deriving next generation organoids.

What are Patient-Derived Xenografts?

Patient-derived xenografts (PDX) are an advanced xenograft model, derived directly from patient tumor tissue and never adapted to grow on plastic (unlike conventional “cell line derived” xenografts). PDX advantages over traditional xenografts include maintaining the genetic features of the parental tumor and reflecting the heterogeneity and diversity of the human patient population.

Within drug development and oncology research PDX have many uses, such as drug efficacy testing (including novel targeted agents due to recapitulating unique clinical features), large scale use in mouse clinical trials to identify responder subgroups, and also for biomarker discovery.

The Importance of PDX in Head and Neck Cancer Research

As well as the points identified above, PDX models have some specific benefits in head and neck cancer research and drug development, particularly for studying radiation response.

Head and Neck Cancer PDX Development and Predictivity

PDX have been developed from a range of tumor types for head and neck cancer. This includes:

  • Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma
  • HPV-negative head and neck squamous cell carcinoma
  • Tumors with rare histologies, such as adenoid cystic carcinoma and midline NUT carcinoma

As for PDX from other cancer types, original tumor genetic and phenotypic characteristics are recapitulated. For head and neck cancer this includes viral oncogene expression in HPV-positive tumors.

Importantly, when treating HPV positive/HPV negative PDX the response is consistent with the clinic, with HPV positive PDX models being more sensitive to radiation treatment. The developed PDX can also be used to predict patient response to targeted agents, allowing studies which are both biologically and clinically relevant.

Orthotopic Head and Neck Cancer PDX Models

Orthotopic head and neck cancer PDX have been shown to provide a more “natural” tumor microenvironment than subcutaneous implantation. This allows for clinically relevant disease development, including metastases to both the lymph nodes and lung for head and neck cancer.

Stromal Composition

PDX models retain their original patient-tumor stromal composition, which plays a key role in tumor viability, cell signaling, and treatment resistance. This means PDX allow more clinically relevant studies, although mouse stroma will begin to dominate following more model passages. Banking of early passage number PDX models is therefore essential to maintain human disease relevant studies.

Radiation Response of Head and Neck Cancer PDX Models

One benefit of using PDX for radiation response studies over murine models is the use of human tumors. There are major differences between human and rodent cells in how they fundamentally regulate response to radiation. Activities and levels of DNA damage response mediators such as DNA-PK, Ku70, and Ku86 differ between species, and human cells are generally more efficient at checkpoint activation and less sensitive to oxidative stress. To make preclinical studies as translatable as possible, using human, clinically relevant cell lines is therefore the best starting point.

PDX models allow radiation response studies, for head and neck cancer as well as looking at simultaneous radio- and chemotherapy treatment, which mimics the clinical setting. For administering radiotherapy, small animal systems provide the opportunity to fractionate the dose given to PDX models e.g. 2 Gy daily fractions mimicking patient treatment. The total radiation dose received by model is, however, usually less than the overall clinical dose.

Organoid Models in Head and Neck Cancer Research

Another key utility of PDX models in head and neck cancer research is that they provide a renewable source of cancer cells for organoid model generation.

Organoids are a novel 3D stem cell culture system, representing miniature imitations of organs. Organoids are derived from self-renewing stem cell populations, which differentiate and organize into a miniature form of an organ, keeping genetic stability intact.

Tumor organoids are derived directly from patient tissue or from PDX models. The major limitations of using patient tissue are access, strict regulations, and a non-renewable tissue source for repeat studies. This is overcome by instead generating tumor organoids from PDX models, which provide expanded availability of models, a wealth of cancer cells, and an enhanced translation from matched in vitro organoids to in vivo PDX.

Organoids derived from head and neck cancer patient tumors recapitulate both molecular, genetic, and morphologic characteristics of the parental tumor, and are currently being used to test radiation sensitizers in head and neck cancer.

Limitations of PDX in Head and Neck Cancer Research

All preclinical models have some limitations, and the drawbacks of PDX in head and neck cancer research are mainly inherently those of PDX.

The models are usually used with immunocompromised mice. This doesn’t provide a host anti-tumoral immune response which is needed for response to chemoradiation, and doesn’t provide a platform for testing immuno-oncology agents. These pitfalls can start to be overcome by using PDX within a humanized mouse model.

PDXs are often established from tissue generated from surgical removal of a tumor. This means you can’t test the PDX in comparison to the patient – to find out if the patient and derived model respond to a treatment in the same way.

Multiple passages can lead to potential biological changes and a loss of stroma in PDX models. This can be overcome by model banking and use at low passage numbers.

Head and neck cancer specific limitations include engraftment rate based on HPV status. HPV-negative tumors engraft marginally better than HPV-positive tumors, and this can be a drawback for studying virally induced disease.

Conclusions

To progress head and neck cancer research, clinically relevant preclinical models such as patient-derived xenografts (PDX) are needed. PDX bring many advantages over historically used in vivo models, and are an excellent gateway to generating next generation models such as tumor organoids.


Related Posts