@article{b3545e3af93e418fa0d1c07d2fef1980,
title = "Y box binding protein 1 inhibition as a targeted therapy for ovarian cancer",
abstract = "Y box binding protein 1 (YB-1) is a multifunctional protein associated with tumor progression and the emergence of treatment resistance (TR). Here, we report an azopodophyllotoxin small molecule, SU056, that potently inhibits tumor growth and progression via YB-1 inhibition. This YB-1 inhibitor inhibits cell proliferation, resistance to apoptosis in ovarian cancer (OC) cells, and arrests in the G1 phase. Inhibitor treatment leads to enrichment of proteins associated with apoptosis and RNA degradation pathways while downregulating spliceosome pathway. In vivo, SU056 independently restrains OC progression and exerts a synergistic effect with paclitaxel to further reduce disease progression with no observable liver toxicity. Moreover, in vitro mechanistic studies showed delayed disease progression via inhibition of drug efflux and multidrug resistance 1, and significantly lower neurotoxicity as compared with etoposide. These data suggest that YB-1 inhibition may be an effective strategy to reduce OC progression, antagonize TR, and decrease patient mortality.",
keywords = "Y box binding protein 1, ovarian cancer, targeted therapy, treatment resistance",
author = "Dhanir Tailor and Angel Resendez and Garcia-Marques, {Fernando Jose} and Mallesh Pandrala and Going, {Catherine C.} and Abel Bermudez and Vineet Kumar and Marjan Rafat and Nambiar, {Dhanya K.} and Alexander Honkala and Le, {Quynh Thu} and Sledge, {George W.} and Edward Graves and Pitteri, {Sharon J.} and Malhotra, {Sanjay V.}",
note = "Funding Information: S.V.M. would like to thank the Translational Oncology Program, Stanford Cancer Institute, for partial support of this work. D.T. would like to thank the Indo-US Science and Technology Forum (IUSSTF) and the Science and Engineering Research Board (SERB), Department of Sciences & Technology, Government of India, for a SERB Indo-US postdoctoral fellowship. A.R. acknowledges support by PA-14-015, grant no. T32 CA 121940, awarded by the Ruth L. Kirschstein National Research Service Award (NRSA). We are grateful to Dr. Manish Chamoli (Buck Institute, CA, USA) and Dr. Erinn Rankin (Stanford University, CA, USA) for providing cells for our studies. The authors acknowledge Dr. Michael R. Eckart and the Protein and Nucleic Acid (PAN) Facility, Stanford University for help in running SPR. Conceptualization, D.T. A.R. V.K. and S.V.M.; methodology, D.T. A.R. F.J.G.-M. M.P. C.C.C. A.B. V.K. M.R. and D.K.N.; statistical analysis, D.T. F.J.G.-M. C.C.C. and D.K.N.; investigation, D.T. A.R. F.J.G.-M. M.P. C.C.C. A.B. V.K. M.R. D.K.N. A.H. G.W.S. Q.-T.L. E.G. and S.J.P.; writing, D.T. A.R. A.H. D.K.N. M.R. S.P. E.G. S.J.P. and S.V.M.; supervision, S.V.M. All authors read and approved the final manuscript. S.V.M. and D.T. are contributors to pending patent number U.S. prov. pat. appln. no. 63/121,674; Filed 4 December 2020 (OHSU Tech ID no. 2964-1). Funding Information: S.V.M. would like to thank the Translational Oncology Program, Stanford Cancer Institute, for partial support of this work. D.T. would like to thank the Indo-US Science and Technology Forum (IUSSTF) and the Science and Engineering Research Board (SERB), Department of Sciences & Technology, Government of India, for a SERB Indo-US postdoctoral fellowship. A.R. acknowledges support by PA-14-015, grant no. T32 CA 121940 , awarded by the Ruth L. Kirschstein National Research Service Award ( NRSA ). We are grateful to Dr. Manish Chamoli (Buck Institute, CA, USA) and Dr. Erinn Rankin (Stanford University, CA, USA) for providing cells for our studies. The authors acknowledge Dr. Michael R. Eckart and the Protein and Nucleic Acid (PAN) Facility, Stanford University for help in running SPR. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
year = "2021",
month = aug,
day = "19",
doi = "10.1016/j.chembiol.2021.02.014",
language = "English (US)",
volume = "28",
pages = "1206--1220.e6",
journal = "Cell Chemical Biology",
issn = "2451-9448",
publisher = "Elsevier Inc.",
number = "8",
}