JAK2, a novel therapeutic target in lung adenocarcinoma?

The field of personalised medicine to provide understanding of the molecular basis of disease is constantly growing. Multiple signalling pathways have been identified that associate with malignant transformation. However, the vast majority of lung cancer patients have no known driver genes detected, and they are still treated with standard cytotoxic chemotherapy. Furthermore, lung cancer ranks the most common cancer worldwide and the 5-year overall survival for patients with non-small cell lung cancer is currently ~11%, mainly due to the difficulty in early diagnosis and the onset of cancer metastasis.

A recent paper in Tumor Biology, “JAK2 variations and functions in lung adenocarcinoma” identifies:

JAK2 as a potential therapeutic target in lung adenocarcinoma.

Upregulation of JAK2 associates with a metastatic phenotype of lung adenocarcinoma which includes lymph node metastases.

JAK2 suppression leads to decreased proliferation, migration and invasion of lung adenocarcinoma cells.

JAK2 may play an important role in lung cancer pathogenesis and high mRNA expression correlated with the presence of lymph node metastasis in patients with lung adenocarcinoma.

The JAK/STAT pathway is required for cell survival and differentiation of many cancers and has emerged as a pivotal participant in biological processes.

This paper highlighted a novel role for JAK2 in lung adenocarcinoma. JAK2 mutations and amplification were detected in plasma of lung adenocarcinoma patients using next generation sequencing. This important finding would potentially make JAK2 a suitable biomarker of disease progression. Furthermore, inhibition of JAK2 using RNAi was found to significantly suppress the proliferation, migration and invasion of non-small-cell lung cancer cells (NSCLC), highlighting JAK2 as a potential therapeutic target in NSCLC.

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Epistem's Models

At Epistem we can offer a validated orthotopic imaging model of non-small-cell lung cancer (JAK2+ A549 cells) for drug development studies. We have extensive experience in in vivo imaging which allows for monitoring of treatment effects in the same animal over time and to detect treatment effects/potentiation and disease regression using single drug or a combination of additional therapeutics, we also have expertise using in vitro proliferation, migration and invasion assays to interrogate treatment mechanisms.

Our pharmacogenomics division has recently developed and validated a genotypic allele burden assay for JAK2V617F that can be performed in our GCLP-accredited laboratory. If you would like a copy of our JAK2V617F data please get in touch and someone will get back to you shortly.

Tumor Biology, “JAK2 variations and functions in lung adenocarcinoma”

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