Technology

Recognition of MUC1-C’s overexpression in cancers is well established. But Genus’ unique approach is new, and offers the potential to significantly advance the treatment of cancer.

The Science: Basic and Applied

The normal physiologic function of MUC1 (Mucin1) is designed to provide a protective barrier for the outer surface of epithelial cells, the cells which form layers both outside and inside organs and body cavities. This barrier prevents caustic elements — toxins, infections, free radicals, acids and other forms of cell stress — from having direct contact with the epithelial cell.

MUC1 proteins are commonly described as hair-like filaments extending on the apical exterior of an epithelial cell. Under stress, the exterior portion of the MUC1 protein, MUC1-N, breaks away.

MUC1: the Intracellular Domain

MUC1-C: the Intracellular Domain

The MUC1 protein also extends across the cell membrane into the cell itself. This intracellular portion, MUC1-C plays a key role in the signaling that increases cell growth activity and protects against cell death.

Tumors have exploited this second role by overexpressing MUC1-C, which dramatically increases cell growth conditions and blocks the cell death pathways used by common anti-cancer drugs. In an epithelial cell exhibiting this phenomenon, MUC1-C is no longer confined to the apical side of the cell. MUC1-C proteins — along with the growth factor receptors which are normally restricted to the basal side of a healthy cell — are overexpressed and radiate from all sides.

Normal epithelium and carcinoma

MUC1-C and Cancer

In brief, MUC1-C receptors are key in facilitating the growth of cancer. MUC1-C:

  • Induces unrestricted growth;
  • Blocks death pathways; and
  • Contributes to metastases.

Common Pharmaceutical Approaches

Other development programs are focused on suppressing tumor growth by directing antibodies or vaccines at MUC1-N. Success to date has been underwhelming using this approach, and tumor growth tends to restart after a short period of suppression. Since the target of these therapies is the ectodomain which cleaves and is shed from the cell, it’s not surprising that affected MUC1-C proteins — still intact in the cytoplasm — soon regenerate and continue the process of tumor cell growth.

the Genus approach