Oncofetal chondroitin sulfate is a highly expressed therapeutic target in non-small cell lung cancer

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Standard

Oncofetal chondroitin sulfate is a highly expressed therapeutic target in non-small cell lung cancer. / Oo, Htoo Zarni; Lohinai, Zoltan; Khazamipour, Nastaran; Lo, Joey; Kumar, Gunjan; Pihl, Jessica; Adomat, Hans; Nabavi, Noushin; Behmanesh, Hakhamanesh; Zhai, Beibei; Dagil, Robert; Choudhary, Swati; Gustavsson, Tobias; Clausen, Thomas M.; Esko, Jeffrey D.; Allen, Jeffrey W.; Thompson, Michael A.; Tran, Nhan L.; Moldvay, Judit; Dome, Balazs; Salanti, Ali; Al-Nakouzi, Nader; Weiss, Glen J.; Daugaard, Mads.

In: Cancers, Vol. 13, No. 17, 4489, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Oo, HZ, Lohinai, Z, Khazamipour, N, Lo, J, Kumar, G, Pihl, J, Adomat, H, Nabavi, N, Behmanesh, H, Zhai, B, Dagil, R, Choudhary, S, Gustavsson, T, Clausen, TM, Esko, JD, Allen, JW, Thompson, MA, Tran, NL, Moldvay, J, Dome, B, Salanti, A, Al-Nakouzi, N, Weiss, GJ & Daugaard, M 2021, 'Oncofetal chondroitin sulfate is a highly expressed therapeutic target in non-small cell lung cancer', Cancers, vol. 13, no. 17, 4489. https://doi.org/10.3390/cancers13174489

APA

Oo, H. Z., Lohinai, Z., Khazamipour, N., Lo, J., Kumar, G., Pihl, J., Adomat, H., Nabavi, N., Behmanesh, H., Zhai, B., Dagil, R., Choudhary, S., Gustavsson, T., Clausen, T. M., Esko, J. D., Allen, J. W., Thompson, M. A., Tran, N. L., Moldvay, J., ... Daugaard, M. (2021). Oncofetal chondroitin sulfate is a highly expressed therapeutic target in non-small cell lung cancer. Cancers, 13(17), [4489]. https://doi.org/10.3390/cancers13174489

Vancouver

Oo HZ, Lohinai Z, Khazamipour N, Lo J, Kumar G, Pihl J et al. Oncofetal chondroitin sulfate is a highly expressed therapeutic target in non-small cell lung cancer. Cancers. 2021;13(17). 4489. https://doi.org/10.3390/cancers13174489

Author

Oo, Htoo Zarni ; Lohinai, Zoltan ; Khazamipour, Nastaran ; Lo, Joey ; Kumar, Gunjan ; Pihl, Jessica ; Adomat, Hans ; Nabavi, Noushin ; Behmanesh, Hakhamanesh ; Zhai, Beibei ; Dagil, Robert ; Choudhary, Swati ; Gustavsson, Tobias ; Clausen, Thomas M. ; Esko, Jeffrey D. ; Allen, Jeffrey W. ; Thompson, Michael A. ; Tran, Nhan L. ; Moldvay, Judit ; Dome, Balazs ; Salanti, Ali ; Al-Nakouzi, Nader ; Weiss, Glen J. ; Daugaard, Mads. / Oncofetal chondroitin sulfate is a highly expressed therapeutic target in non-small cell lung cancer. In: Cancers. 2021 ; Vol. 13, No. 17.

Bibtex

@article{fc3c372d031048a3b911fcd2a4cb603a,
title = "Oncofetal chondroitin sulfate is a highly expressed therapeutic target in non-small cell lung cancer",
abstract = "Broad-spectrum therapeutics in non-small cell lung cancer (NSCLC) are in demand. Most human solid tumors express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that can be detected and targeted with recombinant VAR2CSA (rVAR2) proteins and rVAR2-derived therapeutics. Here, we investigated expression and targetability of oncofetal CS expression in human NSCLC. High oncofetal CS expression is associated with shorter disease-free survival and poor overall survival of clinically annotated stage I and II NSCLC patients (n = 493). Oncofetal CS qualifies as an independent prognosticator of NSCLC in males and smokers, and high oncofetal CS levels are more prevalent in EGFR/KRAS wild-type cases, as compared to mutation cases. NSCLC cell lines express oncofetal CS-modified proteoglycans that can be specifically detected and targeted by rVAR2 proteins in a CSA-dependent manner. Importantly, a novel VAR2-drug conjugate (VDC-MMAE) efficiently eliminates NSCLC cells in vitro and in vivo. In summary, oncofetal CS is a prognostic biomarker and an actionable glycosaminoglycan target in NSCLC.",
keywords = "Chondroitin sulfate, Drug conjugate, Glycosaminoglycan, NSCLC, VDC-MMAE",
author = "Oo, {Htoo Zarni} and Zoltan Lohinai and Nastaran Khazamipour and Joey Lo and Gunjan Kumar and Jessica Pihl and Hans Adomat and Noushin Nabavi and Hakhamanesh Behmanesh and Beibei Zhai and Robert Dagil and Swati Choudhary and Tobias Gustavsson and Clausen, {Thomas M.} and Esko, {Jeffrey D.} and Allen, {Jeffrey W.} and Thompson, {Michael A.} and Tran, {Nhan L.} and Judit Moldvay and Balazs Dome and Ali Salanti and Nader Al-Nakouzi and Weiss, {Glen J.} and Mads Daugaard",
note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
doi = "10.3390/cancers13174489",
language = "English",
volume = "13",
journal = "Cancers",
issn = "2072-6694",
publisher = "M D P I AG",
number = "17",

}

RIS

TY - JOUR

T1 - Oncofetal chondroitin sulfate is a highly expressed therapeutic target in non-small cell lung cancer

AU - Oo, Htoo Zarni

AU - Lohinai, Zoltan

AU - Khazamipour, Nastaran

AU - Lo, Joey

AU - Kumar, Gunjan

AU - Pihl, Jessica

AU - Adomat, Hans

AU - Nabavi, Noushin

AU - Behmanesh, Hakhamanesh

AU - Zhai, Beibei

AU - Dagil, Robert

AU - Choudhary, Swati

AU - Gustavsson, Tobias

AU - Clausen, Thomas M.

AU - Esko, Jeffrey D.

AU - Allen, Jeffrey W.

AU - Thompson, Michael A.

AU - Tran, Nhan L.

AU - Moldvay, Judit

AU - Dome, Balazs

AU - Salanti, Ali

AU - Al-Nakouzi, Nader

AU - Weiss, Glen J.

AU - Daugaard, Mads

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - Broad-spectrum therapeutics in non-small cell lung cancer (NSCLC) are in demand. Most human solid tumors express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that can be detected and targeted with recombinant VAR2CSA (rVAR2) proteins and rVAR2-derived therapeutics. Here, we investigated expression and targetability of oncofetal CS expression in human NSCLC. High oncofetal CS expression is associated with shorter disease-free survival and poor overall survival of clinically annotated stage I and II NSCLC patients (n = 493). Oncofetal CS qualifies as an independent prognosticator of NSCLC in males and smokers, and high oncofetal CS levels are more prevalent in EGFR/KRAS wild-type cases, as compared to mutation cases. NSCLC cell lines express oncofetal CS-modified proteoglycans that can be specifically detected and targeted by rVAR2 proteins in a CSA-dependent manner. Importantly, a novel VAR2-drug conjugate (VDC-MMAE) efficiently eliminates NSCLC cells in vitro and in vivo. In summary, oncofetal CS is a prognostic biomarker and an actionable glycosaminoglycan target in NSCLC.

AB - Broad-spectrum therapeutics in non-small cell lung cancer (NSCLC) are in demand. Most human solid tumors express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that can be detected and targeted with recombinant VAR2CSA (rVAR2) proteins and rVAR2-derived therapeutics. Here, we investigated expression and targetability of oncofetal CS expression in human NSCLC. High oncofetal CS expression is associated with shorter disease-free survival and poor overall survival of clinically annotated stage I and II NSCLC patients (n = 493). Oncofetal CS qualifies as an independent prognosticator of NSCLC in males and smokers, and high oncofetal CS levels are more prevalent in EGFR/KRAS wild-type cases, as compared to mutation cases. NSCLC cell lines express oncofetal CS-modified proteoglycans that can be specifically detected and targeted by rVAR2 proteins in a CSA-dependent manner. Importantly, a novel VAR2-drug conjugate (VDC-MMAE) efficiently eliminates NSCLC cells in vitro and in vivo. In summary, oncofetal CS is a prognostic biomarker and an actionable glycosaminoglycan target in NSCLC.

KW - Chondroitin sulfate

KW - Drug conjugate

KW - Glycosaminoglycan

KW - NSCLC

KW - VDC-MMAE

U2 - 10.3390/cancers13174489

DO - 10.3390/cancers13174489

M3 - Journal article

C2 - 34503301

AN - SCOPUS:85114308055

VL - 13

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 17

M1 - 4489

ER -

ID: 280070467