GEN Exclusives

More »

BioMarket Trends

More »
Oct 15, 2009 (Vol. 29, No. 18)

Firms Seek to Prove Cancer Stem Cell Hypothesis

CSCs Are Believed Responsible for Tumorigenesis, Metastases, and Recurrence of Disease

  • The pharmaceutical and biotech industries have begun to develop targeted inhibitors of pathways that contribute to tumorigenesis and metastasis. These new medicines offer the promise of treating many types of cancer with greater efficacy and fewer unwanted side effects than heretofore possible. An important premise guiding this work is the cancer stem cell (CSC) hypothesis.

    While normal stem cells are essential for development, play a key role in tissue maintenance, and aid in repair, cancer stem cells are believed responsible for tumorigenesis, metastases, and cancer recurrence. The first report providing evidence of CSCs identified primitive leukemic cells that could give rise to acute myeloid leukemia in immunodeficient mice.

    Since that discovery in 1994, these cells have been found in most solid tumors. Skeptics of the CSC hypothesis have argued that cancer cells may be capable of de-differentiating and that isolation methods for CSCs do not select for all cells with the capacity for self-renewal. Regardless, the hypothesis provides an explanation for differences between cells in a tumor and offers a new rationale for drug design.

    Moving from concept to clinic in just over a decade, CSC research has uncovered several promising pathways that a growing number of biopharmaceutical companies are exploring in clinical and preclinical studies.

  • Notch Pathway

    The Notch pathway is an evolutionarily conserved system that regulates cell fate during development and in the adult. Its involvement in cancer depends upon its role in normal cells of that same tissue. If Notch acts as a gatekeeper of stem cells or regulator of precursor cell fate under normal conditions, it acts as an oncogene in promoting malignant growth. On the other hand, it is a tumor suppressor in tissues in which it normally initiates terminal differentiation.

    Different points in the pathway have been targeted for drug development. OncoMed Pharmaceuticals’ OMP-21M18 is an antibody that blocks signals by binding to Delta-like ligand. The drug, which is in a clinical trial involving patients with advanced solid tumors, is part of a $1.4 billion collaboration with GlaxoSmithKline.

    Merck and Roche have inhibitors to γ-secretase that cleaves the Notch receptor releasing the Notch intracellular domain, a transcription factor. Both companies’ drugs are in early testing against solid tumors. Finally, Trojantec is targeting the Notch pathway with a truncated version of Mastermind, a coactivator involved in chromatin-specific transcription. The drug may prove useful against tumors that overexpress Notch signaling components.


Add a comment

  • You must be signed in to perform this action.
    Click here to Login or Register for free.
    You will be taken back to your selected item after Login/Registration.

Related content

Jobs

GEN Jobs powered by HireLifeScience.com connects you directly to employers in pharma, biotech, and the life sciences. View 40 to 50 fresh job postings daily or search for employment opportunities including those in R&D, clinical research, QA/QC, biomanufacturing, and regulatory affairs.
 Searching...
More »

GEN Poll

More » Poll Results »

Climate Change and Disease

Are the incursions of dengue fever and West Nile virus into North America just the tip of the iceberg of insect-borne diseases that are migrating due to a warming planet?