Problem

The loss or mutation of serine/threonine kinase 11 (STK11), observed in 20–25% of non-small cell lung cancer (NSCLC) cases, is associated with poor prognosis and resistance to immune checkpoint blockade (ICB). While STK11 alterations are commonly linked to immunotherapy resistance, some STK11-mutant tumors may still respond favorably to ICB. Additionally, STK11 loss appears to influence both prognosis and response to chemotherapy. These complexities underscore the need for reliable biomarkers to predict patient sensitivity to immunotherapy and guide personalized treatment plans

Solution

• STK11 loss affects lineage plasticity in murine models and multi-lineage de-differentiation (MLDD) phenotypes in patients. Researchers at Ohio State University have developed “STK11-MLDD”, a STK11 Multi-Lineage De-Differentiation Classifier that applies a validated gene signature to assess functional STK11 loss, then uses additional biomarkers to assign patients to one of three groups: “Neuroendocrine,” “TTF1-Low,” and TTF1-Positive”, which differ in their response to immunotherapy, composition of the tumor microenvironment and inflammation status
• The differentiation subgroups of STK11-MLDD have significant prognostic and predictive effects based on outcomes in patient cohorts and application of this classifier on randomized clinical trial data

Applications

Use the STK11 Multi-Lineage De-Differentiation Classifier as a clinically actionable biomarker to identify the three key tumor phenotypes of NSCLC, which can guide patient selection for clinical trials and the creation of precision treatment strategies

Advantages

• STK11-MLDD classifier accurately identifies functional loss of STK11 in tumors in which no mutations were detected on sequencing
• Identification of differentiation phenotypes is currently dependent on histopathological evaluation, which is an imperfect tool and not well suited for clinical biomarker development, while STK11-MLDD offers a standardized classification tool based on measured gene expression levels
• STK11-MLDD is highly predictive of immune exclusion and NSCLC patient outcomes

Seeking opportunities for co-development, out-licensing or new venture formation