Preclinical cancer model spotlight: August edition

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 biotechs need to now plan their preclinical studies more efficiently than ever.

In our new blog series, we’ll be highlighting 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. EGFR triple mutant NSCLC PDX model with Osimertinib resistance

Our August model spotlight starts with this EGFR triple mutant NSCLC PDX model with Osimertinib resistance.

• Patient information

This PDX model was developed from a biopsy sample taken from a 54-year-old man who had stage IV primary bronchogenic carcinoma/adenocarcinoma in his left upper lung.

• Drug Treatment history

Initially the patient’s tumour was characterised by a deletion in exon 19 of the EGFR gene but on treatment with Erlotinib, the patient acquired an additional mutation at position 790 (T790M). On subsequent treatment with Osimertinib, the patient developed resistance by acquiring a third mutation at position 797 (C797S).

• Histology analysis

This PDX model is characterised by a poorly-moderately differentiated adenocarcinoma as shown by the histology images below.

• Genetic profile

Next-generation sequencing shows that the PDX model has an EGFR genetic profile of 45.9% exon 19 deletion, 17.37% T790M and 16.73% C797S.

Model drug treatment data

This model has been tested for its response to a number of different therapeutics and has shown resistance to Erlotinib and AZD9291 (Osimertinib) when administered as single agents, as well as in combination.

In addition, the model shows resistance to Cetuximab and EAI045 as both individual agents and when given in combination. On the other hand, it is sensitive to Brigatinib and has been shown to successfully reverse the effect of drug resistance when treated with Brigatinib in combination with Cetuximab.

Want more information or access to this model?

Request more information or get in touch with our experts via our Cancer Models Platform.

2. Ovarian cancer PDX model with clinical platinum and PARP inhibitor resistance

Next up is this ovarian cancer PDX model with clinical platinum and PARP inhibitor resistance.

• Model establishment

To develop this model, a biopsy was taken from a 62-year-old female patient whose stage IV ovarian high-grade serous carcinoma had metastasized to her liver. The PDX model is of adenocarcinoma subtype.

• Patient treatment history

As you can see from the graph below, the patient had received five lines of treatment over the course of four years, including Niraparib, Olaparib, Paclitaxel and Bevacizumab. The patient’s tumour was resistant to both platinum agents and PARP inhibitors.

• Model drug treatment

The PDX model has also been validated for its PARP inhibitor resistance by administering Olaparib as part of an efficacy study as shown in the graphs below.

Want more information or access to this model? Request more information or get in touch with our experts via our Cancer Models Platform.

3. EGFR overexpressing cell lines with either T790M or L858R EGFR mutations

• Cell line establishment

These overexpressing EGFR cell lines have been created by cloning MCF10A parent cells – a human mammary gland epithelium cell line that is non-tumourigenic – with full length human, sequence-validated ORFs.

Characterisation

For these T790M and L858R over-expressing EGFR cell lines, the following data is available to ensure each has the right molecular phenotype for your preclinical study:

• Sequencing of the mutant EGFR gene inserted into the parent cell line genome
• Real-time PCR and western blot expression
• Proliferation and morphology analysis
• QC testing for viruses, mycoplasma and sterility

Drug treatment response

Both T790M and L858R EGFR cell lines have been tested for their response to common therapeutic agents, including Gefitinib and Osimertinib as shown in the dose-response curves below.

Want more information or access to this model? Request more information or get in touch with our experts via our Cancer Models Platform.

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

We have over 6,500 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.

Image credit: Alinenok sourced from Unsplash

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