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Approximately 25% of breast cancer
patients have over-amplification of the Her-2-neu gene, a member of the epidermal growth factor
(EGF) family of receptor tyrosine kinases, correlating with poor prognosis.
Interestingly, among aggressive hormonally driven solid tumors such as ovarian, breast, and
prostate cancer, studies have shown increased expression of the bombesin (BBS)-like peptide
hormone, gastrin-releasing peptide (GRP) and its cognate receptor, GRP receptor (GRPR).
We hypothesize that the EGFR family, including Her-2-neu synergize with GRPR to develop the
metastatic phenotype.
Specific molecular targeting of breast
cancers with Her-2-neu over-expression is moderately therapeutic in the metastatic setting and
unknown in the adjuvant setting. The elucidation of EGFR trans-activation by GRPR should
facilitate the rational design of combination drug regimens for the tumors that are most
elusive to current therapeutics. The long-term goal of my laboratory is to elucidate the
molecular mechanisms regulating development of the metastatic phenotype prior to the
development of large volume disease, thereby tailoring specific combination treatment options
in the adjuvant setting. |
