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Insulin-Like Growth Factor Protein 3 (IGF-BP3) and related methods for inhibiting tumor growth

Summary

Lead Inventors: lrena Kirman, MD, Ph.D. and Richard L. Whelan, MDTechnology to be Commercialized: This invention provides a method of preventing the proliferation of metastases andrecurrence of cancer following open surgical resection of tumor mass. This is accomplished by monitoringand modulating the levels of the 43-45kD protein insulin-like growth factor binding protein-3 (IGFBP-3),the major insulin-like growth factor binding protein, in the patient's circulation. Following open surgery, aconsiderable percentage of patients develop metastases from tumor cells that persist in tissue microfocior in the circulation after tumor resection. Paradoxically, it is believed to be the trauma of open surgeryitself which temporarily provides an opportunity of cancer recurrence; surgical trauma has been shown toalter the proliferative capacity of sera for tumor cells. This correlates with a decrease of circulating levelsof IGFBP-3.IGFBP-3 is a natural pro-apoptotic and is anti-proliferative factor for tumor cells. Its declinefollowing surgery appears to be due to proteolytic cleavage mediated by matrix metalloproteinase 9(MMP-9). Correspondingly serum levels of MMP-9 are significantly elevated after open surgery, beinginduced by inflammation-related stimuli. IGFBP-3 degradation fragments do not possess tumor cellgrowth regulatory effects of the intact protein which thus permits the metastases to take hold.The technology presented here provides methods for administration of a patient-specific,temporally defined dosage regime of IGFBP-3 during the perioperative period for the purpose ofdecreasing the potential of postoperative metastases occurring. By restoring endogenous circulatingIGFBP-3 to presurgery levels, it is anticipated this will reduce or potentially eliminate proliferation ofmetastatic cells after open surgery tumor resection and therefore help prevent post-surgical recurrence ofcancer.Efficacy of this technology is supported by findings from in vitro experiments, clinical samplemeasures and animal model studies.Studies to date have focused on colorectal cancer but other solid tumor cancers, including thoseof the prostate, breast and lung, are being studied. IGFBP-3 regulation could be a broadly applicabletherapeutic approach to prevent solid tumor recurrence. Since this therapy restores a naturally occurringfactor, it presents a safe option for combinatorial use in conjunction with radiotherapy or anti-tumor drugs.

Technology Benefits

Novel approach to prevent occurrence of metastases following solid tumor resection Can potentially be utilized in open surgery procedures for an array of solid tumors IGBP-3 a potentially good candidate for adjuvant therapy with radiotherapy or tumor-specific drugs

Technology Application

Novel approach to prevent occurrence of metastases following solid tumor resection Can potentially be utilized in open surgery procedures for an array of solid tumors IGBP-3 a potentially good candidate for adjuvant therapy with radiotherapy or tumor-specific drugs

Detailed Technology Description

None

*Abstract

None

*Inquiry

Sara Gusik Columbia Technology Ventures Tel: (212) 854-8444 Email: TechTransfer@columbia.edu

*IR

1642

*Principal Investigator

*Publications

Surgery (2004) 136 (2): 205-9; Disease of the Colon and Rectum (2004) 47(6): 91 1-1 8; Surg Endosc. (2005)19(1):55-9

*Web Links

"Use of insulin-like growth factor binding protein 3 (IGF-BP3) for inhibition of: USPTO issued patentUSPTO: US20060084603

Country/Region

USA