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New Lung Cancer Cell Lines for a Diverse Patient Cohort

May 25, 2021 1:00:00 PM / by David Deems

A diverse patient cohort for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) accounts for around 85% of all cases of lung cancer which in turn is the cancer responsible for most deaths – around 1.8 million worldwide in 20201. NSCLC has proven relatively amenable to stratification and the development of targeted therapies with research efforts continuing to further extend and refine these approaches. Our four new models for lung cancer will directly support this work by providing access to stable, authenticated models for a diverse patient cohort. In total we now offer five models for NSCLC – Jacket, Bastion, Boulder, Pincer and Throne. 

Developing precision therapies for NSCLC

Therapies for NSCLC are differentiated in line with tumor subtype – whether adenocarcinoma or squamous cell – and with respect to targeting mutations driving cancer cell proliferation and tumor growth. For example, agents targeting EGFR, ALK, ROS1 and BRAF genetic mutations are already approved2. KRAS mutations are extremely common, particularly in adenocarcinomas and an important target for ongoing research. Better surgical practice and the potential for liquid biopsies is making it easier for clinicians to ensure rigorous tumor characterization but the identification of personalized drug therapies is very much a work in progress.

The five lung cancer cell models we now offer are all from patients over 60 years old with a long history of smoking, though duration and consumption vary (full details are documented). Notable features differentiating the cohort are detailed below:

  • Throne had a previous diagnosis of melanoma with current status unknown
  • Jacket was taking no prescribed medications at the time of diagnosis
  • Pincer, Boulder and Bastion do not have a KRAS mutation; Jacket and Throne do
  • Bastion has no reported genetic mutations
  • Jacket has a neurotrophic receptor tyrosine kinase (NRTK) gene fusion.

These differences and others make it easier for researchers to test drug response as a function of genetic and epigenetic variability. The information we supply with our models includes a drug response report which in the case of the lung cancer cohort shows how our cancer models can differentiate the potential efficacy of therapies targeting specific genetic mutations.

Assessing drug response with patient-specific models

The panel of drugs used to develop the drug response report for our lung cancer patient cohort consists of etoposide, cisplatin, larotrectinib, and erlotinib. Etoposide is one of around ten drugs prescribed routinely for NSCLC3 while cisplatin is used for a range of cancers, often as a combination therapy to overcome drug resistance. Larotrectinib and erlotinib are both targeted therapies for patients with an NTRK gene fusion and a KRAS mutation, respectively. Jacket has both of these mutations and is therefore potentially a candidate for either therapy. 

 

Jacket Drug Response For Erlotinib and Larotrectinib 

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The drug response curves for Jacket, for both larotrectinib and erlotinib are shown above. These indicate that Jacket is more sensitive to erlotinib, identifying it as the drug with greater potential efficacy. This is valuable, clinically relevant information that directly illustrates the utility of patient-specific models. Furthermore, the KRAS mutation is common to many cancers and targeted therapies such as erlotinib therefore have broad potential application. Testing drug response with an appropriate model identifies patient populations that may respond well, facilitating the transfer of a successful therapy from one cancer type to another while at the same time reducing the risk of waiting for treatment of human patients in clinical trials. 

Find out more about our lung cancer models or view the associated drug response report here. 

 

1 WHO Cancer Fact Sheet Detail. 3rd March 2021. Available to view at: https://www.who.int/news-room/fact-sheets/detail/cancer

2 Editor’s Pick ‘Precision Medicine in Lung Cancer’ 8th Jan 2020. Available to view at: https://www.emjreviews.com/oncology/article/precision-medicine-in-lung-cancer/

3 Chemotherapy for Non-Small Cell Lung Cancer https://www.cancer.org/cancer/lung-cancer/treating-non-small-cell/chemotherapy.html

Topics: Lung Cancer Cell Models, Drug Response Data

David Deems

Written by David Deems