April 11, 2022 – Mount Sinai researchers have developed a new method to identify aggressive lung cancers at an early stage and target drugs known as aurora kinase inhibitors to tumors that are particularly susceptible to answer it. The findings, published in Nature Communication on March 24, could lead to major advances in the treatment of lung adenocarcinoma, the most common type of lung cancer.
The Mount Sinai team used a genomic network model to measure tumor invasiveness – distinguishing aggressive tumors from so-called ‘indolent’ tumors, which often cannot be distinguished by a chest CT scan – and identify which ones will respond to aurora kinase inhibitors, molecules that can inhibit gene signature regulators.
“Approaches to the diagnosis and treatment of early-stage lung adenocarcinoma are evolving and are based on advances in understanding the biology and clinical activities of these tumors,” said lead author Charles Powell, MD, MBA, Janice and Coleman Rabin Professor of Medicine and Chief of Pulmonary, Critical Care, and Sleep Medicine at Icahn Medical School at Mount Sinai. “Our work using novel network approaches, in collaboration with Sema4, to identify signatures of invasiveness and to identify drugs that can intercept the progression of these cancers should help advance understanding and outcomes for this cancer.”
The research team used a genetically modified mouse model to define the role of aurora kinases in early disease progression. They performed molecular profiling of early-stage lung cancer samples with RNA sequencing and identified signature genes associated with tumor invasiveness. Sema4 researchers used novel genomic networking approaches to identify key network regulators and therapeutic drugs to demonstrate that targeting the signaling pathway reduces the spread of lung cancer and improves survival. They identified and tested aurora kinase inhibitors, including AMG900, as an effective treatment to intercept lung cancer progression in models.
The researchers encourage further validation and clinical trials in human tumors. Future studies should examine the possibilities of similarly intervening in signaling by immune cells or other cells in the surrounding tumor stroma, the researchers said, because cancer progression relies on the interaction between cells. tumor and surrounding cells.
Researchers from Weill Cornell Medicine-NewYork-Presbyterian Hospital and Sema4, a patient-centric health intelligence company, contributed to this study. This work was supported by grants from the National Institutes of Health (R01CA163772, R01HL130826, and R01CA240342), New York State Stem Cell Science Program (C34052GG), American Thoracic Society Foundation-Unrestricted Grant (ATS-2017-24) , from the American Lung Association of the Northeast Lung Cancer Discovery Award (LCD-504985) and the Department of Defense (W81XWH-19-1-0613).
For more information: https://www.mountsinai.org
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