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Research Advances from the Acquired Resistance to Therapy Network (ARTNet)

Using patient samples, functional screening, molecular studies, and clinically relevant models, ARTNet investigators revealed mechanisms of treatment resistance and identified strategies to overcome them.

Mechanistic and Translational Studies of Acquired Drug Resistance

By analyzing drug responses in acute myeloid leukemia (AML) patient samples and using experimental models, researchers at the OHSU ARTNet Center found that CDK4/6 inhibition can suppress an adaptive response to venetoclax and enhance its activity. 

Investigators with the BAATAAR-UP ARTNet Center found that BRAF class II/III non-small cell lung cancer (NSCLC) can escape pan-RAF inhibition through ARAF-KSR1 signaling and showed that RAS or MEK inhibition co-targeting is effective against this resistance mechanism. 

Building on fundamental research, investigators with the OHSU ARTNet Center completed a Phase I clinical trial, which tested ruxolitinib (a Janus kinase inhibitor) in combination with venetoclax (a BCL2 inhibitor) in patients with relapsed/refractory AML. They found that this treatment approach was safe and well tolerated for patients, as well as identified CD56 as a potential biomarker of resistance. 

Technology Development for Drug Resistance Studies

ARTNet researchers generated the Biomedical Data Manifest to improve the transparency, documentation, and reuse of biomedical datasets for artificial intelligence (AI)/machine learning (ML) applications.  

Researchers with the H-CARR ARTNet Center developed a spatial T cell receptor (TCR) profiling approach, which revealed how local tumor environments shape T cell states in head and neck cancer. 

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