Connecting biopharmas with the right preclinical cancer models and CRO partners

Cancer Models Forum

Posted by Henrietta, November 2020

November Model Spotlight

As part of our commitment to the preclinical oncology community, we want to go one step further to support pharma and biotech researchers during this difficult time. With many scientists around the world returning to the laboratory at reduced capacity or working complex shift patterns, pharma and biotechnology companies need to now plan their preclinical studies more efficiently than ever.

In this blog series, we highlight a selection of popular, interesting and uncommon models available from our specialist CRO partners, which might be of interest for your upcoming studies. And we’re providing insight into the molecular, patient, drug response, histology and growth curve data available for each – information that is currently only available to the enterprise users of our Cancer Models Platform.

1. Triple hit lymphoma PDX model with rituximab resistance

  • Significance

MYC/BCL2/BCL6 triple hit lymphoma is a rare subset of high-grade B-cell lymphoma with very aggressive clinical behaviour. Treatment of patients with standard chemotherapy is associated with poor outcome and a median overall survival of around 18 months. Novel therapy options are therefore urgently needed for this type of lymphoma.

  • Patient information

This PDX model was developed from a recurring stage IV diffuse large B-cell lymphoma (DLBCL) with germinal centre B-cells (GCB) as the cells of origin (COO) and was isolated from a peripheral blood sample of a female patient.

  • Drug Treatment history

After diagnosis of the lymphoma, the patient underwent a CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy regimen. Following disease recurrence, one cycle of R-DHAP (rituximab; dexamethasone, cytarabine, cisplatin) and one cycle of R-ICE (rituximab; ifosfamide, carboplatin, etoposide) was administered.

  • Flow-cytometry analysis

The tumour sample was characterized by flow cytometry directly after isolation and stained positively for CD19, CD10, CD38, CD79 and CD22 whereas CD20, CD11c, CD5, CD43, CD25, CD23, CD103 and FMC7 were absent. CD20 expression was lost during the course of the rituximab therapy.

  • Histology image of the subcutaneous PDX model in NMRI-nude mice

EPO Histology

Lymphoma PDX: Passage 3, H&E Staining

  • Genetic profile

FISH (Fluorescence in situ hybridization) analysis revealed rearrangements in the MYC, BCL2 and BCL6 genes (“triple-hit lymphoma”).

  • Gene expression analysis

Illumina® RNA-seq data are available for this model upon request.

  • Drug treatment response

This model has been tested for its response to a number of different chemotherapeutics including cyclophosphamide, vincristine, everolimus, methotrexate and gemcitabine. Tumor growth was progressing upon treatment with everolimus and methotrexate (RTV>1.2), whereas treatment with cyclophosphamide, vincristine or gemcitabine led to a partial remission (RTV<0.7).

Drug treatment response

Drug treatment (Passage 5)

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2. NSCLC rat PDX model

  • Patient information

This rat PDX model was developed from an invasive primary tumour in a 54-year-old Caucasian male with non-small-cell lung adenocarcinoma in a bronchus and lung site.

  • PDX establishment

Patient surgery completed on 11th March 2017. The tumour was implanted into the bilateral hind flank of a rat SRG model over the course of a 40 min transplant time.

Hera Pdx Establishment

  • Histology

The tumour stained TTF1 positive and P40 negative.

Hera histology

  • Genetic profile

A NGS panel of 6000 genes was conducted to characterize the patient tumour samples and patient derived xenografts (PDX). A sequence of 17 established NSCLC associated genes was analysed and the sample was found to carry a Tyr1248His homozygous mutation in the MET gene that was preserved in passages P0, P1 and P2 and is present in the tyrosine kinase region. This mutation is likely pathogenic as somatic variant Tyr1248Asp and Tyr1248Cys are reported in HGMD in Papillary renal carcinoma patients.

  • Drug treatment response

This model has been tested for its response to Cisplatin + Docetaxel, which led to reduction in tumour growth.

Hera drug treatment response

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3. NSCLC PDX models with crizotinib sensitivity

  • Patient information

This PDX model was developed from a 47-year-old female with bronchogenic lung cancer. The PDX model pathology is poorly differentiated adenocarcinoma.

  • Histology

LIDE histology

  • Genetic profile

PDX model NGS and IHCdata revealed EML4-ALK fusion, EGFR(+++) and c-MET(++).

  • Drug treatment response

This model has been tested for its response to crizotinib, and results showed high sensitivity with significant reduction in tumour volume.

LIDE drug treatment response

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Want to see which models on our Cancer Models Platform match your search criteria?

We have over 8,000 preclinical cancer models from specialist CROs around the globe in our world-leading inventory. See which models have the right molecular phenotype for your study by searching on our Cancer Models Platform.

Model data, growth curves and histology images shared with permission from our CRO partners

Header image credit: Alinenok sourced from Unsplash