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TGen Wins $2M NIH Grant for Blood-Based Melanoma Monitoring Approach

NEW YORK (GenomeWeb) — The Translational Genomics Research Institute (TGen) announced this week that it has been awarded a five-year grant worth $2 million from the National Institutes of Health to assess a blood-based method for monitoring metastatic melanoma.

The project — being led by TGen's Muhammed Murtaza — aims to use circulating tumor DNA (ctDNA) to monitor drug response and resistance in metastatic melanoma patients in order to guide treatment decisions.

"To monitor melanoma during treatment, the only available test today is imaging, such as a CT scan," Murtaza said in a statement. "But you can't scan patients very often during treatment because it's expensive and exposes patients to radiation. If we can develop a blood test to monitor treatment response, we may be able to use it weekly."

With the NIH funding, Murtaza and collaborators will analyze serial plasma, tumor, and germline samples from metastatic melanoma patients from three cohorts: a completed anti-PD-1 immunotherapy trial; a collection from the Stand Up To Cancer Genomically Enabled Medicine for Melanoma trial; and a prospective observational study at Mayo Clinic Arizona that is evaluating standard of care immunotherapy and molecularly targeted drugs.

According to the grant's abstract, the investigators will use tumor exome sequencing to identify patient-specific mutations and targeted digital sequencing to quantify ctDNA. Changes in ctDNA levels during treatment will be compared with tumor response and progression as assessed by imaging.

Additionally, tumor exome sequencing will be compared with exome sequencing of pre-treatment plasma DNA to determine the concordance of plasma and tumor samples, and exome sequencing of post-treatment plasma DNA will be used to identify genomic alterations that occur during disease progression in patients receiving immunotherapy.

The researchers also aim to identify genomic drivers of acquired resistance to anti-PD-1 treatment by examining molecular pathways that are recurrently altered at disease progression.

The project is expected to help establish whether ctDNA analysis is effective for melanoma monitoring and can serve as an alternative to tumor re-biopsies for patient selection, and if it can help investigate the mechanisms underlying acquired immunotherapy resistance, the abstract states.

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