Summary of Invention
This invention provides a novel target for the treatment of carcinomas of the upper aerodigestive tract (UADT) with squamous cell origin, including head and neck cancers (HNC), and lung cancers (LC).
Using positional cloning, MSKCC investigators have identified a new gene, which they named SCCRO (Squamous-cell carcinoma related oncogene), in a genetic location that is significantly amplified in 40 percent of UADT, cervical, and ovarian carcinomas. SCCRO contains a basic helix-loop-helix zip motif as a transcription factor, possibly as an inducer of angiogenesis. SCCRO transfection into 3T3 cells results in growth advantages in serum-deficient conditions; increased invasive potential; colony formation ability in soft agar; and tumor formation in nude mice, indicating its oncogenic potential.
Moreover, high-level expression of SCCRO in primary tumors is associated with increased rates of locoregional metastasis and an adverse clinical outcome in UADT carcinomas. In vivo, SCCRO expression is significantly correlated with nodal metastasis in patients with HNC, establishing a critical role for MMP2 (matrix metalloproteinase-2) in SCCRO-associated invasion. In support of the biological association, a significant high-level correlation has been demonstrated between the expression of SCCRO and MMP2 in primary LC cases. Moreover, SCCRO and MMP2 expression was associated with a poor clinical outcome. SCCRO antisense and sRNA experiments in cells with overexpressed SCCRO have already validated the use of this target in certain cancer cells.
Lead Inventor
Dr. Bhuvanosh Singh
Patent Information
US patent prosecution ongoing.
References
Contact Information
Julia Calonge, PhD
Tel: 212-639-6181; Fax: 212-717-3934
E-mail: calongej@mskcc.org
