ALK-P (ALK Pathways)
Research type
Research Study
Full title
Detecting molecular pathways which are key in the pathogenesis ALK- positive cancers
IRAS ID
324010
Contact name
Sam Khan
Contact email
Sponsor organisation
University of Leicester
Duration of Study in the UK
3 years, 11 months, 24 days
Research summary
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. We will explore the cellular mechanisms involved in changes driven by EML4-ALK that could lead to identification of new targetable pathways, using patient samples obtained from those who have EML4-ALK lung cancers. This approach will support an evidence-based rationale for stratification of EML4-ALK positive lung cancer patients to particular treatment protocols.
REC name
London - South East Research Ethics Committee
REC reference
22/PR/1711
Date of REC Opinion
10 Jan 2023
REC opinion
Favourable Opinion