American Association for Cancer Research
crc-23-0044_fig6.png (217.39 kB)

FIGURE 6 from Proteogenomic Approaches for the Identification of NF1/Neurofibromin-depleted Estrogen Receptor–positive Breast Cancers for Targeted Treatment

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posted on 2023-07-26, 14:20 authored by Beom-Jun Kim, Ze-Yi Zheng, Jonathan T. Lei, Matthew V. Holt, Anran Chen, Jianheng Peng, Diana Fandino, Purba Singh, Hilda Kennedy, Yongchao Dou, María del Rosario Chica-Parrado, Emmanuel Bikorimana, Dan Ye, Yunguan Wang, Ariella B. Hanker, Nada Mohamed, Susan G. Hilsenbeck, Bora Lim, Jaya Ruth Asirvatham, Arun Sreekumar, Bing Zhang, George Miles, Meenakshi Anurag, Matthew J. Ellis, Eric C. Chang

Assess the impact of NF1 protein levels on treatment responses in patient tumors. A, NF1 protein levels quantified by KIPA SureQuant (normalized by TIC) in each of the biopsy (orange circles) from a given POL patient were plotted and median is marked by a solid blue line. Blue and red dotted lines mark 75% and 25% quartile, respectively. The latter corresponds to 0.6 fmol/TIC. B, Tumors stratified by the 0.6 fmol/TIC cutoff were defined as NF1-high and NF1-low and their Ki67 levels pre-and post-letrozole treatment were plotted. P values were determined by paired t test.


HHS | National Institutes of Health (NIH)

U.S. Department of Defense (DOD)

Cancer Prevention and Research Institute of Texas (CPRIT)

Breast Cancer Research Foundation (BCRF)



A major challenge for targeting the consequence of tumor suppressor disruption is the accurate assessment of protein functional inactivation. NF1 can repress both RAS and ER signaling, and a ComboMATCH trial is underway to treat the patients with binimetinib and fulvestrant. Herein we report a MS-verified NF1 IHC assay that can determine a threshold for NF1 loss to predict treatment response. These approaches may be used to identify and expand the eligible patient population.