@article{9d80524821734c75b70d71878a3948d2,
title = "Genomics, morphoproteomics, and treatment patterns of patients with alveolar soft part sarcoma and response to multiple experimental therapies",
abstract = "Overexpression of transcription factor 3 in alveolar soft part sarcoma(ASPS) results in upregulation of cell proliferation pathways. No standard treatment algorithm exists for ASPS; multikinase inhibitors[tyrosine kinase inhibitor (TKI)] and immune checkpoint inhibitors (ICI) have shown clinical benefit. To date, no studies have reported on management strategies or sequencing of therapy. We evaluated ASPS treatment patterns and responses in an experimental therapeutics clinic. Genomic and morphoproteomic analysis was performed to further elucidate novel targets. We retrospectively reviewed patients with ASPS treated on clinical trials. Demographic and clinical next-generation sequencing (NGS) profiles were collected. AACR GENIE database was queried to further evaluate aberrations in ASPS. Morphoproteomic analysis was carried out to better define the biology of ASPS with integration of genomic and proteomic findings. Eleven patients with ASPS were identified; 7 received NGS testing and mutations in CDKN2A (n = 1) and hepatocyte growth factor (n = 1) were present. Ten patients were treated with TKIs with stable disease as best response and 4 patients with ICI (three partial responses). Within GENIE, 20 patients were identified harboring 3 called pathogenic mutations. Tumor mutation burden was low in all samples. Morphoproteomic analysis confirmed the expression of phosphorylated c-Met. In addition, fatty acid synthase and phosphorylated-STAT3 were detected in tumor cell cytoplasm and nuclei. Patients with ASPS have a quiescent genome and derive clinical benefit from VEGF-targeting TKIs. Morphoproteomic analysis has provided both additional correlative pathways and angiogenic mechanisms that are targetable for patients with ASPS. Our study suggests that sequential therapy with TKIs and immune checkpoint inhibitors is a reasonable management strategy.",
author = "Roman Groisberg and Jason Roszik and Conley, {Anthony P.} and Lazar, {Alexander J.} and Portal, {Daniella E.} and Hong, {David S.} and Aung Naing and Herzog, {Cynthia E.} and Neeta Somaiah and Zarzour, {Maria A.} and Shreyaskumar Patel and Brown, {Robert E.} and Vivek Subbiah",
note = "Funding Information: A.P. Conley is a consultant at Bayer, Deciphera, and Genentech. D.S. Hong is a consultant at Alpha Insights, Axiom, Janssen, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, Trieza, Adaptimmune, Baxter, Bayer, Genen-tech, GLG, Group H, Guidepoint Global, Infinity, reports receiving a commercial research grant from Abbvie, Adaptimmune, Genmab, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, Medimmune, Mirati, Amgen, MiRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle Genetics, Takeda, AstraZeneca, Bayer, BMS, Daiichi-Sanko, Eisai, Fate Therapeutics, Genentech, and reports receiving other commercial research support from LOXO, MiRNA, ASCO, AACR, SITC, Genmab, has ownership interest (including patents) in Molecular Match, OncoResponse, and Presagia. A. Naing reports receiving a commercial research grant from NCI, EMD Serono, Regeneron, Merck, BMS, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab, MedImmune, PsiOxus, Immune Deficiency Foundation, Healios Onc. Nutrition, Atterocor, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, has received speakers bureau honoraria from CytomX Therapeutics and Novartis, and has provided expert testimony for ARMO BioSciences (travel and accommodation). C.E. Herzog is a member, data monitoring committee at Merck, Sharp, and Dome and reports receiving a commercial research grant from Roche Genentech and Array Biopharm. S. Patel is a consultant at Novartis, Epizyme, Daiichi Sankyo, Dova, Bayer and reports receiving a commercial research grant from Blueprint Medicines. V. Subbiah is a consultant/advisory board member at LOXO Oncology/Eli Lilly, Helsinn, R-Pharma US, Incyte, QED, Novartis, Medimmune and reports receiving a commercial research grant from LOXO Oncology/Eli Lilly, Blueprint Medicines, Fujifilm, Pharmamar, D3, Pfizer, Multi-vir, Amgen, ABBVIE, Agensys, Boston Biomedical, Idera, Turning Point therapeutics, Exelixis, Inhibrx, Altum, Medimmune, Dragonfly Therapeutics, Takeda, Roche/Genentech, Novartis, Bayer, GSK, Nanocarrier, Berghealth, Incyte, and North-west Biotherapeutics. No potential conflicts of interest were disclosed by the other authors. Funding Information: The University of Texas MD Anderson Cancer Center is supported by the NIH Cancer Center Support Grant CA016672. V. Subbiah acknowledges the Shannon Wilkes Sarcoma Research funds. This work was supported in part by Cancer Prevention Research Institute of Texas Grant RP110584 and National Center for Advancing Translational Sciences Grant UL1 TR000371 (Center for Clinical and Translational Sciences). We thank the patients and their families for enrolling in clinical trials. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = may,
day = "1",
doi = "10.1158/1535-7163.MCT-19-0579",
language = "English (US)",
volume = "19",
pages = "1165--1172",
journal = "Molecular cancer therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "5",
}