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#9 - A tumor diagnostic marker for new blood vessels formation which can be used for early detection of brain tumors
Long Title: Differential gene expression in physiological and pathological angiogenesis
NIH Reference No.: E-285-2006
Executive Summary
General Description
As a tumor expands in size, portions of the tumor grow beyond the reach of existing blood vessels which supply the tumor with nutrients and oxygen. The lack of oxygen in these regions of the tumor triggers the release from the tumor factors which stimulate the formation of new blood vessels, a process known as angiogenesis. Angiogenesis inhibitors act to prevent this process, disrupting the tumor vasculature and limiting its growth. Angiogenesis inhibitors are believed to have great potential as new anti-cancer agents, and are the focus of extensive development.
Scientific Progress
The invention describes specific markers that can be used to differentiate between tumor angiogenesis and physiological angiogenesis, which may be useful for diagnosis and therapeutic targeting of tumor vessels. This invention also describes several organ-specific endothelial markers that could aid in the selective delivery of therapeutics to specific anatomical sites, such as brain and liver tissues. Such specificity is important in order to minimize the potential side effects (cross-reactivity with off-target tissues). These markers could also have significant diagnostic utility. There are several advantages to targeting tumor vessels rather than the tumor cells themselves. Tumor cells are genetically unstable, and tumor markers are typically only elevated in a fraction of samples. Because tumor endothelium is derived from stable diploid host cells, these markers may be useful for detecting or treating a large variety of tumor types. Also, tumor vessels may be less likely to develop resistance towards tumor vessel-targeted agents, as these cells are genetically stable. Targeting the vessels also obviates a number of drug delivery problems associated with targeting the tumor cells, especially for high molecular-weight compounds that have difficulty penetrating tumors.
Future Direction
Strengths
Weaknesses
Patent Status
Canadian Application No. 2,669,260 filed June 28, 2007
Australian Application No. 2014200453 filed Jan. 28, 2014
US Application No. 13/863,674 filed Apr. 16, 2013
U.S. Pat: 8,440,411 issued May 14, 2013
Relevant Publications
Chaudhary A, et al. Cancer Cell. 2012 Feb 14;21 (2):212-26 (PMID: 22340594)
Seaman S, et al. Cancer Cell. 2007 Jun;11 (6):539-54 (PMID: 17560335)
Inventor Bios
Brad St. Croix, Ph.D.
Dr. Brad St. Croix received his Ph.D. in Medical Biophysics from the University of Toronto in 1998 under Dr. Robert S. Kerbel. He trained as a post-doctoral fellow in the laboratory of Dr. Bert Vogelstein at Johns Hopkins University under a fellowship from the National Cancer Institute of Canada. In 2002, he established the Tumor Angiogenesis Group at the Center for Cancer Research, NCI. His laboratory focuses on the identification of molecules involved in human tumor angiogenesis and utilizes mouse models to translate new molecular information on angiogenesis into the development of novel diagnostics and therapeutics for cancer.
NIH Reference No.: E-285-2006
Executive Summary
- Invention Type: Class III Diagnostics, Therapeutics
- Patent Status: PCT Application No. PCT/US2007/072395, US Application No. 60/879,457, 60/858,068, 13/863,674, 12/514,297.U.S. Pat: 8,440,411 issued - US Patent issued in 2013, Patents pending in US, Canada, and Australia
- LINK: https://www.google.com/patents/US8440411?dq=8,440,411&hl=en&sa=X&ei=ODqvU5XBCsyNyAT_poDIDg&ved=0CBwQ6AEwAA
- NIH Reference Number: E-285-2006
- NIH Institute or Center: National Cancer Institute (NCI)
- Disease Focus: Solid tumors, preferentially brain or liver endothelial tumors
- Basis of Invention: Tissue-specific vascular marker proteins
- How it works: Anti-angiogenic agent attached or bound to binding agent that selectively targets organ-specific endothelial marker proteins
- Lead Inventor: Brad St. Croix, Ph.D.
- Development Stage: In vitro and in vivo available
- Novelty: Highly selective marker proteins for pathological angiogenesis
- Clinical Application: Potential uses include:
- Early diagnostic for many types of brain or liver tumors to prevent surgery or reduce tumor recurrence
- Tracking agent for tumor development
- Therapeutic to inhibit tumor growth
General Description
As a tumor expands in size, portions of the tumor grow beyond the reach of existing blood vessels which supply the tumor with nutrients and oxygen. The lack of oxygen in these regions of the tumor triggers the release from the tumor factors which stimulate the formation of new blood vessels, a process known as angiogenesis. Angiogenesis inhibitors act to prevent this process, disrupting the tumor vasculature and limiting its growth. Angiogenesis inhibitors are believed to have great potential as new anti-cancer agents, and are the focus of extensive development.
Scientific Progress
The invention describes specific markers that can be used to differentiate between tumor angiogenesis and physiological angiogenesis, which may be useful for diagnosis and therapeutic targeting of tumor vessels. This invention also describes several organ-specific endothelial markers that could aid in the selective delivery of therapeutics to specific anatomical sites, such as brain and liver tissues. Such specificity is important in order to minimize the potential side effects (cross-reactivity with off-target tissues). These markers could also have significant diagnostic utility. There are several advantages to targeting tumor vessels rather than the tumor cells themselves. Tumor cells are genetically unstable, and tumor markers are typically only elevated in a fraction of samples. Because tumor endothelium is derived from stable diploid host cells, these markers may be useful for detecting or treating a large variety of tumor types. Also, tumor vessels may be less likely to develop resistance towards tumor vessel-targeted agents, as these cells are genetically stable. Targeting the vessels also obviates a number of drug delivery problems associated with targeting the tumor cells, especially for high molecular-weight compounds that have difficulty penetrating tumors.
Future Direction
- The lab is using several genetically-engineered mouse models to understand the functional role of these tumor endothelial markers (TEMs) in vivo.
- They are also developing novel therapeutics, such as neutralizing antibodies, in order to block angiogenesis and tumor growth.
Strengths
- Endothelial markers are highly organ-specific, and thus can serve as promising targets for selective delivery of molecular medicines; for example, the marker CD276 is undetectable during normal physiological angiogenesis, but is over-expressed during tumor angiogenesis.
Weaknesses
- Need data to confirm the consistent staining of TEM markers in tumor vasculature of brain cancers
- Need to focus panel of markers for diagnostic use to one or several specific markers
Patent Status
Canadian Application No. 2,669,260 filed June 28, 2007
Australian Application No. 2014200453 filed Jan. 28, 2014
US Application No. 13/863,674 filed Apr. 16, 2013
U.S. Pat: 8,440,411 issued May 14, 2013
Relevant Publications
Chaudhary A, et al. Cancer Cell. 2012 Feb 14;21 (2):212-26 (PMID: 22340594)
Seaman S, et al. Cancer Cell. 2007 Jun;11 (6):539-54 (PMID: 17560335)
Inventor Bios
Brad St. Croix, Ph.D.
Dr. Brad St. Croix received his Ph.D. in Medical Biophysics from the University of Toronto in 1998 under Dr. Robert S. Kerbel. He trained as a post-doctoral fellow in the laboratory of Dr. Bert Vogelstein at Johns Hopkins University under a fellowship from the National Cancer Institute of Canada. In 2002, he established the Tumor Angiogenesis Group at the Center for Cancer Research, NCI. His laboratory focuses on the identification of molecules involved in human tumor angiogenesis and utilizes mouse models to translate new molecular information on angiogenesis into the development of novel diagnostics and therapeutics for cancer.