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Journal article
Targeting the unfolded protein response, XBP1, and the NLRP3 inflammasome in fibrosis and cancer
Cancer biology & therapy, v 15(4), pp 452-462
04 Feb 2014
PMID: 24496016
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Increasing health care costs in the US are due in a large part to the increasing prevalence of chronic diseases in an aging population. Current therapeutic strategies for treating chronic diseases alleviate symptoms allowing patients to live longer with these diseases, but they do little, however, to alter the underlying disease course. Recent advances in molecular biology are revealing new drug targets that may significantly alter the course of these diseases and, as a result, offer economic relief from burgeoning health care costs. Endoplasmic reticulum (ER) stress has been implicated as an underlying pathology in many chronic diseases, and, therefore, the development of therapies designed to ameliorate ER stress may yield novel, effective treatment strategies. Herein, we report that X-box binding protein 1 (XBP1) may be one of the earliest proteins engaged in response to ER stress. We show that a new signaling peptide derived from the ER-embedded transient receptor potential calcium channel protein 1 (TRPC1) engages XBP1 upstream of NLRP3 inflammasome-mediated maturation and secretion of IL-1β/IL-18. Moreover, we show that a synthetic homolog of this signaling peptide (Naclynamide™) administered intravenously twice weekly over a 4-week treatment course induced suppuration and evoked partial or complete resolution of lesions associated with a fibrotic granuloma, a lymphosarcoma, and a colo-rectal carcinoma in canine patients. The mode of action for Naclynamide™ as a first-in-class anti-cancer drug candidate is discussed.
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Details
- Title
- Targeting the unfolded protein response, XBP1, and the NLRP3 inflammasome in fibrosis and cancer
- Creators
- Beth Overley-Adamson - Center for Animal Referral and Emergency Services (CARES); Langhorne, PA USA.Carol M Artlett - Drexel UniversityConnie Stephens - TherimuneX PharmaceuticalsSihem Sassi-Gaha - Drexel UniversityRansome D Weis - Doylestown HospitalJames D Thacker - TherimuneX Pharmaceuticals (United States)
- Publication Details
- Cancer biology & therapy, v 15(4), pp 452-462
- Publisher
- Landes Bioscience
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000333558000014
- Scopus ID
- 2-s2.0-84897498263
- Other Identifier
- 991019168381104721
UN Sustainable Development Goals (SDGs)
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- Web of Science research areas
- Oncology