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Spotting a malignant signature

Apr 17, 2019

New algorithm identifies patients with a targetable genomic defect found in many cancers

APRIL 17, 2019, New York—Medications known as PARP inhibitors have emerged as a promising therapy for several forms of cancer that are fueled by a defect in the cells’ DNA repair machinery. Yet many people with cancers caused by the defect, known as HR deficiency, remain unidentified because standard genetic panels used in the clinic do not reliably detect the defect. Now, a team led by Ludwig Harvard Investigator Peter Park has designed an algorithm that can successfully “read” the molecular signature of the cancer-driving defect and identify patients who might benefit from treatment with PARP inhibitors.

If incorporated into standard gene panel tests, the researchers said, the algorithm could expand greatly the pool of patients who stand to benefit from these therapies. Their study appears in the current issue of Nature Genetics.

“Pinpointing actionable genetic biomarkers and treating patients with drugs that specifically target the relevant cancer-driving pathways is at the heart of precision medicine. We believe our algorithm can greatly enhance physicians’ ability to deliver such individualized therapy,” said study senior author Peter Park, who is also a professor of biomedical informatics in the Blavatnik Institute at Harvard Medical School.

The advantage of the new algorithm is that it can see the molecular footprints of the HR defect even in standard clinical tests, which analyze only a subset of genes. The researchers say their algorithm is better at detecting the presence of HR defects because it was “trained” on thousands of fully sequenced tumor genomes.

The HMS release from which this summary is derived can be found here.