Anti-Cancer Agents that Inhibit Cell Motility, Angiogenesis, and Metastasis
Background:
The National Cancer Institute's
Urologic Oncology Branch is seeking statements of capability or
interest from parties interested in collaborative research to
further develop, evaluate, or commercialize anti-cancer
drugs.
Technology:
The Grb2 protein, through its SH2
domain, mediates growth factor driven cell motility in vitro
and angiogenesis in vivo. This invention describes potent,
highly selective antagonists of Grb2 SH2 domain binding that have
been shown to block cell motility stimulated by several growth
factors including hepatocyte growth factor (HGF) and vascular
endothelial cell growth factor (VEGF). Because the ability of these
growth factors to initiate increased cell motility is frequently
linked to tumor metastasis, the antagonists described in this
technology have the potential to improve cancer survival rates by
inhibiting metastasis. Additionally, they potently inhibit HGF and
VEGF-stimulated morphogenesis and angiogenesis. This discovery is
significant because HGF's signaling pathway is frequently
over-activated in numerous human cancers, including colon, gastric,
breast, lung, thyroid and renal carcinomas, melanoma, several
sarcomas as well as glioblastoma.
The small, synthetic Grb2 SH2 domain antagonists have already been
shown to inhibit metastasis of melanoma and prostate cancer-derived
tumor cells in mice. These results establish a critical role for
Grb2 SH2 domain-mediated interactions during metastasis and support
the efficacy of this class of compound in reducing the spread of
solid tumors in humans.
Further R&D
Needed:
- Formulation for oral availability and improved biological
half-life.
- Pharmacodynamic marker development.
- Combination with other targeted anti-cancer drugs in
preclinical models.
R&D Status:
In vitro proof-of-concept in models of tumor cell invasion
and angiogenesis;
In vivo proof-of-concept in animal models
of prostate and melanoma metastasis
IP Status:
PCT Patent Application No. PCT/US2007/078494 filed 14 Nov. 2007
Value Proposition:
- Potential to improve cancer survival rates by inhibiting cell
motility, tumor angiogenesis and tumor metastasis.
- Novel mechanism to reduce the spread of solid tumors and treat
numerous types of cancers.
Contact
Information:
John D. Hewes, Ph.D., NCI
Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov
Reference: #670 MC
Posted 06/12/08