Inhibition of tumor growth using compounds that inhibit QSOX1 enzymatic activity

Douglas Lake (Inventor)

Research output: Patent

Abstract

Despite tremendous scientific progress and treatment advances, cancer continues to be the leading cause of death worldwide, with global burden by 2030 estimated to be 21.4 million new diagnoses and 13.2 million deaths (IARC). Because invasion and metastasis are arguably the most dangerous characteristics of cancer, therapeutics that suppress these characteristics could be very valuable. Quiescin sulfhydryl oxidase1 (QSOX1) is an enzyme that is highly overexpressed in many tumor types but not in normal cells or tissue. Research has shown that QSOX1 over-expression plays an important role in tumorigenesis, cell invasion/migration and metastases. Suppression of QSOX1 protein expression leads to reduced tumor cell growth and invasion in vitro and in vivo. Researchers at Arizona State University have discovered that QSOX1 is a tractable anti-neoplastic drug target and have identified and characterized compounds which inhibit the enzymatic activity of QSOX1. These compounds slow the growth and invasion of pancreatic, renal and breast cancer cells in murine models of cancer, likely by disrupting the extracellular matrix and tumor-stroma interaction. Further, these compounds could sensitize tumors such that other therapeutic agents are more effective or could be used in lower doses. Currently, no other small molecule inhibitors exist for QSOX1, making these first-in-class. Since surgery would cure cancer if it did not metastasize, drugs that suppress extracellular matrix deposition and metastases represent a new class of anti-neoplastic agent. Potential Applications Treatment or prognosis of tumors that over-express QSOX1 (non-limiting tumor types: pancreatic, lung, colon, breast and prostate tumors) oReduce/slow the increase in tumor mass oDiminish tumor cell viability oSuppress metastasis oLimit/prevent/inhibit worsening/reduce recurrence of symptom development oIncrease survival time Benefits and Advantages Less expensive than biologics Can be modified to increase bioavailability Suppresses metastatic tumor growth Dowload Original PDF For more information about the inventor(s) and their research, please see Dr. Laeke's directory webpage
Original languageEnglish (US)
StatePublished - Apr 15 2015

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