Biomarker Discovery and Development

Colon Cancer (CC) Biomarkers

Opportunity and Potential Impact

Transformation of the stem and epithelial cells lining the colon and rectum leads to the development of colorectal cancer, the second leading cause of all cancer related deaths in the US.  Recent studies from several laboratories provide compelling evidence that the growth, spreading, and therapeutic resistance of many cancers involves “cancer stem cells”.  As a result, great interest has developed in the identification and characterization of these stem cells, as well as, developing new therapeutic targeting approaches aimed at these cells in particular.  However, defining the molecular species/molecular signatures/biomarkers which comprise and may be utilized to identify GI stem cells and epithelial cell lineages derived from them, as well as factors that cause or are a marker of their cancerous transformation and development of cancer stem cells, remains a challenge due to the following factors:

  •  an inadequate understanding of GI stem cells

  • inadequate understanding of the molecular mechanisms of epithelial lineage differentiation and growth regulation in the GI tract

  • a lack of methods to isolate intestinal stem cells and maintain them in long term culture without transformation

  • the inability to procure large uniform homogeneous and sustainable quantities of non-transformed intestinal stem and epithelial cell lineages, as well as, cancer stem cells

  • an inability to efficiently characterize and compare intestinal stem/progenitor cells and derived epithelial lineages in both normal and malignant conditions.

AlfaGene Bioscience, Inc. has developed a unique system for the isolation and long term culturing of adult human intestinal stem cells and the ability to direct these stem cells to differentiate and create functional epithelial cell types representative of the endogenous GI epithelium. Furthermore, aided by this novel technology, AlfaGene has demonstrated the ability to produce paired stem cell lines and derived epithelial cells obtained via concurrent isolation of tumor-initiating cancer stem cells and unaffected normal adult stem cell counterparts from biopsies from the same individual’s colon during routine colonoscopies.  This capability allows for the direct comparison of cellular, molecular, and genetic differences between intestinal stem cells from different tissues, disease states, and individuals, as well as developing paired stem cells from tumorogenic and normal colonic cells from the same individual.  Thus, enabling, hitherto unattainable, large scale production and supply of homogeneous cells of specific (uncontaminated with other cells) cell types and with minimal genetic background variation.  Thereby, dramatically reducing inherent variability issues while greatly enhancing efficiency and specificity of analyses.