{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:15:17Z","timestamp":1790644517397,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers13174489","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T10:59:12Z","timestamp":1630925952000},"page":"4489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Oncofetal Chondroitin Sulfate Is a Highly Expressed Therapeutic Target in Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Htoo Zarni","family":"Oo","sequence":"first","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Lohinai","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, National Koranyi Institute of Pulmonology, 1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nastaran","family":"Khazamipour","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9053-8853","authenticated-orcid":false,"given":"Gunjan","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Pihl","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Adomat","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noushin","family":"Nabavi","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-9483","authenticated-orcid":false,"given":"Hakhamanesh","family":"Behmanesh","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-0716","authenticated-orcid":false,"given":"Robert","family":"Dagil","sequence":"additional","affiliation":[{"name":"Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Gustavsson","sequence":"additional","affiliation":[{"name":"Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Clausen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Esko","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Allen","sequence":"additional","affiliation":[{"name":"Kootenai Health, Post Falls, ID 83854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Aurora Cancer Care, Advocate Aurora Health, Milwaukee, WI 53215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhan L.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Mayo Clinic, Scottsdale, AZ 85259, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Moldvay","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, National Koranyi Institute of Pulmonology, 1122 Budapest, Hungary"},{"name":"MTA-SE NAP, Brain Metastasis Research Group, Department of Pathology, Hungarian Academy of Sciences, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balazs","family":"Dome","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, National Koranyi Institute of Pulmonology, 1122 Budapest, Hungary"},{"name":"Department of Thoracic Surgery, National Institute of Oncology, Semmelweis University, 1122 Budapest, Hungary"},{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Salanti","sequence":"additional","affiliation":[{"name":"Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Al-Nakouzi","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada"},{"name":"Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-597X","authenticated-orcid":false,"given":"Glen J.","family":"Weiss","sequence":"additional","affiliation":[{"name":"MiRanostics Consulting, Oro Valley, AZ 85755, 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