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Novel therapeutic and diagnostic approaches for EML4-ALK driven lung cancer


   Molecular and Cell Biology

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  Prof A Fry  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Lung cancer is the largest cause of cancer-related deaths in the UK and worldwide. While little progress has been made in long-term survival rates, we now have a good understanding of the genetic drivers raising the prospect of earlier diagnosis and more effective treatments. Around 5% of lung cancers are driven by expression of the EML4-ALK oncogenic fusion and this genetic change is commonly seen in younger patients without a history of smoking. While many of these patients initially respond well to targeted ALK inhibitors, some patients show little or no response and all patients inevitably relapse. Hence, there is an urgent need to better understand resistance mechanisms to ALK inhibitors in lung cancer patients and develop new therapeutic and diagnostic approaches. 

We have recently discovered a novel pathway that potentially drives the metastatic dissemination of EML4-ALK positive cancers. This pathway involves formation of a complex between EML4-ALK and the NEK9 and NEK7 kinases, and the subsequent stabilization of microtubules. We hypothesise that in turn this leads to changes in actin organization, altered cell morphology and increased cell migration. In this project - funded through the Leicester Precision Medicine Institute (LPMI) - the PhD student will be trained in cutting edge discovery and translational cancer research. They will explore the cellular mechanisms involved in changes driven by EML4-ALK that could lead to identification of new targetable pathways, test whether activation of these pathways may lead to increased sensitivity to particular drugs, and develop a novel mass spectrometry-based diagnostic approach to the identification of EML4-ALK oncogenic fusions. This will then be tested using patient samples obtained from those who have EML4-ALK lung cancers. Together, these approaches will support an evidence-based rationale for stratification of EML4-ALK positive lung cancer patients to particular treatment protocols.

Entry requirements

UK Bachelor’s Degree with at least 2:1 in a relevant subject or overseas equivalent. 

University of Leicester English language requirements apply where applicable

To apply, please follow the guidance at:

https://le.ac.uk/study/research-degrees/funded-opportunities/lpmi-fry-2021


Funding Notes

This 3-year LPMI Studentship provides:
• UK/EU tuition fee waiver
• Annual stipend at UKRI rates (£15,609 for 2021/22)

References

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