Lead Inventors: lrena Kirman, MD, Ph.D. and Richard L. Whelan, MD
Prevention of proliferation of metastases and recurrence of cancer following open surgical resection of tumor mass:
This invention provides a method of preventing the proliferation of metastases and
recurrence of cancer following open surgical resection of tumor mass. This is accomplished by monitoring
and 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, a
considerable percentage of patients develop metastases from tumor cells that persist in tissue microfoci
or in the circulation after tumor resection. Paradoxically, it is believed to be the trauma of open surgery
itself which temporarily provides an opportunity of cancer recurrence; surgical trauma has been shown to
alter the proliferative capacity of sera for tumor cells. This correlates with a decrease of circulating levels
of IGFBP-3.
IGFBP-3 is a natural pro-apoptotic and is anti-proliferative factor for tumor cells. Its decline
following 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, being
induced by inflammation-related stimuli. IGFBP-3 degradation fragments do not possess tumor cell
growth 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 of
decreasing the potential of postoperative metastases occurring. By restoring endogenous circulating
IGFBP-3 to presurgery levels, it is anticipated this will reduce or potentially eliminate proliferation of
metastatic cells after open surgery tumor resection and therefore help prevent post-surgical recurrence of
cancer.
Efficacy of this technology is supported by findings from in vitro experiments, clinical sample
measures and animal model studies.
Studies to date have focused on colorectal cancer but other solid tumor cancers, including those
of the prostate, breast and lung, are being studied. IGFBP-3 regulation could be a broadly applicable
therapeutic approach to prevent solid tumor recurrence. Since this therapy restores a naturally occurring
factor, it presents a safe option for combinatorial use in conjunction with radiotherapy or anti-tumor drugs.
Applications:
• 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
Advantages:
• 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
Patent Status: United States Issued Patent# 7166,288 and patent pending
Licensing Status: Available for Licensing and Sponsored Research Support
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