Molecular characterization of the Ras-MAPK pathway in Metastatic Breast Cancer


Justin Wayne Wong Tiulim, Jun Yin, Joanne Xiu, Wolfgang Michael Korn, Heinz-Josef Lenz, Gino Kim In, Evanthia T. Roussos Torres, Janice M. Lu, Darcy V. Spicer, Bing Xia, Dave S. B. Hoon, Elisa Krill-Jackson, Arielle Lutterman Heeke, Sarah Sammons, Claudine Isaacs, Foluso Olabisi Ademuyiwa, Cynthia X. Ma, Antoinette R. Tan, Irene Kang

Background: The Ras-MAPK pathway is a known driver of tumorigenesis and therapeutic target in a variety of cancers. Alterations in this pathway have been linked to decreased tumor immunogenicity. However, molecular alterations in the Ras-MAPK are rare in breast cancer (BC) and their clinical implications remain unclear. As mutational status does not accurately correlate with transcriptional activity, a MAPK pathway activity score (MPAS, Wagle et al., 2018, npj Precision Medicine) is indicative of MAPK activation and correlates with response to MEK (MEKi) or BRAF inhibition (BRAFi). Our goal was to determine the frequency of molecular alterations in the Ras-MAPK and correlate to MAPK pathway activation in MBC.

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