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Ref Type Journal Article
PMID (27784746)
Authors Tian X, Nguyen M, Foote HP, Caster JM, Roche KC, Peters CG, Wu P, Jayaraman L, Garmey EG, Tepper JE, Eliasof S, Wang AZ
Title CRLX101, a Nanoparticle-Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α.
Journal Vol Issue Date Pages Journal Short Title
Cancer research 77 1 2017 Jan 01 112-122 Cancer Res
URL
Abstract Text Novel agents are needed to improve chemoradiotherapy for locally advanced rectal cancer. In this study, we assessed the ability of CRLX101, an investigational nanoparticle-drug conjugate containing the payload camptothecin (CPT), to improve therapeutic responses as compared with standard chemotherapy. CRLX101 was evaluated as a radiosensitizer in colorectal cancer cell lines and murine xenograft models. CRLX101 was as potent as CPT in vitro in its ability to radiosensitize cancer cells. Evaluations in vivo demonstrated that the addition of CRLX101 to standard chemoradiotherapy significantly increased therapeutic efficacy by inhibiting DNA repair and HIF1α pathway activation in tumor cells. Notably, CRLX101 was more effective than oxaliplatin at enhancing the efficacy of chemoradiotherapy, with CRLX101 and 5-fluorouracil producing the highest therapeutic efficacy. Gastrointestinal toxicity was also significantly lower for CRLX101 compared with CPT when combined with radiotherapy. Our results offer a preclinical proof of concept for CRLX101 as a modality to improve the outcome of neoadjuvant chemoradiotherapy for rectal cancer treatment, in support of ongoing clinical evaluation of this agent (LCC1315 NCT02010567). Cancer Res; 77(1); 112-22. ©2016 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
NLG207 NLG207 0 2
Drug Name Trade Name Synonyms Drug Classes Drug Description
NLG207 IT-101|EP0057|CRLX101 NLG207 (CRLX101) is a nanoparticle conjugated to camptothecin, which inhibits topoisomerase-1 and HIF1-alpha, which may increase sensitivity to chemoradiation, and may result in tumor growth inhibition (PMID: 27784746, PMID: 33390325, PMID: 33632874).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References