Researchers from Thomas Jefferson University have discovered that the protein guanylyl cyclase C (GCC) is expressed in humans solely in the intestines, including the colon and rectum, making it a selective marker for colorectal tumors that
Researchers from Thomas Jefferson University have discovered that theprotein guanylyl cyclase C (GCC) is expressed in humans solely in the intestines,including the colon and rectum, making it a selective marker for colorectaltumors that metastasize. These findings appear in the December 10th issueof the Proceedings of the National Academy of Sciences.
The research, led by Scott Waldman, MD, PhD, associate professor ofmedicine, biochemistry and molecular pharmacology and acting director ofthe division of clinical pharmacology, is groundbreaking because it hasthe potential to lead to the first effective way of detecting colorectaltumors once they spread beyond the intestines.
"The survival rate for patients who have metastatic colorectalcancer is presently very poor, with only 5% surviving after five years,because there has not been an effective way of tracking its spread to otherorgans and present chemotherapy does not make an enormous impact,"explains Dr. Waldman. "Knowing that GCC is specific to the intestinesallows us to use it as a tag or marker to detect where the cancer has spread."
Protein Expressed Only in Normal and Malignant Intestinal Cells
By examining human tissue samples with the reverse transcription-polymerasechain reaction (RT-PCR), researchers discovered that GCC is expressed onlyby two different cells in the body. It is present in the single layer ofcells that lines the normal intestine and continues to be expressed afterthese cells undergo malignant transformation and migrate out of the intestinesinto other sites. As a result of this, GCC acts as a marker, demarcatingthe cancer's spread throughout the body.
Guanylyl cyclase C also is the receptor for the heat-stable enterotoxin(ST) produced by Escherichia coli. With this working knowledge, the Jeffersonteam exposed preparations of human tissues to ST and discovered that theonly tissues that interact with this small protein were those that expressedGCC. Only tissues outside the intestine, containing metastatic colorectalcancer, expressed GCC and interacted with ST.
"We found that ST effectively binds to GCC in all tissues whichcontained metastatic colorectal cancer, regardless of the type of tissueor its location," says Dr. Waldman. "It is our hope that thisresearch leads to new treatments that use ST as a guided missile to targetcancer-fighting poisons directly to metastatic tumor cells, without harmingnormal surrounding tissues."
Diagnostic Tests and Therapies in the Works
Targeted Diagnostics and Therapeutics, Inc, a biotechnology companythat has acquired the worldwide exclusive license to the work from Dr.Waldman's laboratory, is laying the groundwork for the birth of new diagnosticand therapeutic options by developing a tissue biopsy test that will accuratelystage patients to determine whether colorectal cancer has spread outsideof the intestine. The company is also developing a blood test that willdetermine whether colorectal cancer has spread beyond the intestine orhas recurred after definitive surgery. In addition, work has begun on newtherapeutics that will use ST to target and kill metastatic colorectalcancer cells.
"It is our goal to make diagnostic tests available for clinicaluse in the next two to three years, reducing the number of lives colorectalcancer claims each year, which is currently close to 50,000," saysHarry A. Arena, CPA, MBA, President and CEO of Targeted Diagnostics andTherapeutics.