BACKGROUND:  Cervical cancer is the second most common cancer responsible for cancer-related deaths in women around the world. The incidence is increasing, with 450,000 new cases diagnosed annually worldwide. Currently, cervical cancer is commonly diagnosed by screening pap smears for abnormal cells. A cervical biopsy can then aid in the determination of the nature of these abnormal cells, indicating whether or not they should be removed. However, these current methods do not provide information concerning the potential aggressiveness of cancers resulting from these abnormalities. Before progressing to tumors, the earliest stage of cervical cancer is characterized by an abnormality known as cervical intraneoplasia (CIN). It would be beneficial to be able to reliably diagnose and understand the potential invasiveness of the cervical cancer at this stage so that proper treatment could begin as early as possible.

INNOVATION:  Researchers at UCLA have demonstrated that cystatin E/M gene expression can be used as a diagnostic tool for cervical cancer development at the earliest stage. It has previously been identified that the expression of cystatin E/M protein was reduced in cancer cell lines. In CINs, cystatin E/M is expressed, but this expression is lost in tumors. In addition, cancer aggressiveness correlates to the level of reduction or loss of cystatin E/M, which in turn results in the overexpression of the target protein cathepsin L, providing diagnostic markers for cervical cancer. Furthermore, potential therapy for cervical cancer is the introduction of cystatin E/M as a systemic treatment. Small molecule inhibitors of cathepsin L could also provide cervical cancer therapies.

POTENTIAL APPLICATIONS 

• Cervical and ovarian cancer diagnostics
• Oncology therapeutics
• Protein therapeutics

ADVANTAGES

• Early cancer diagnosis using a genetic marker
• Ability to understand potential invasiveness at the earliest stage of the cancer
• The same principle could be applied for other cancer types

DEVELOPMENT-TO-DATE:  Thirty different cervical tumors, thirty ovarian cancers, and normal control tissues were analyzed for the expression of cystatin E/M. High expression of this protein was observed in all of the normal tissues, but loss of expression was seen in more than 75% of the cancerous tissues demonstrating its diagnostic utility. Functional inactivation of cystatin E/M by point mutations on cathepsin L binding sites has been confirmed. Animal studies that determine the efficacy of cystatin E/M as a therapeutic agent are planned.

Related Papers (Selected)

• Veena, M.S.; Lee. G.; Keppler. D.; Mendonca, M.S.; Redpath, J.L.; Stanbridge, E.J.; Wilczynski, S.P.; Srivatsan, E.S. Genes, Chromosomes, & Cancer 2008, 47, 740-754. [more]