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Basic science of HER-2/neu: a review.

M C Hung¹, Y K Lau

¹Department of Cancer Biology, the University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

Seminars in Oncology

|September 11, 1999

Summary

Targeting the HER-2/neu oncogene, overexpressed in many cancers, offers a promising strategy for developing new anticancer therapies. Inhibiting HER-2/neu, particularly in breast cancer, suppresses tumor growth and enhances survival.

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Area of Science:

Oncology
Molecular Biology
Cancer Genetics

Background:

The HER-2/neu (c-erbB-2) oncogene, part of the epidermal growth factor receptor family, is overexpressed in various human cancers, including breast, ovarian, lung, gastric, and oral cancers.
HER-2/neu overexpression in breast cancer correlates with reduced survival and enhanced malignancy and metastasis.
While its role in chemoresistance is debated, HER-2/neu overexpression is linked to resistance in some contexts.

Purpose of the Study:

To review signal transduction pathways of the HER-2/neu receptor tyrosine kinase.
To summarize strategies for targeting HER-2/neu-overexpressing cancer cells.
To evaluate novel therapeutic approaches for HER-2/neu-driven cancers.

Main Methods:

Targeting the HER-2/neu promoter using cationic liposomes or adenovirus vectors to deliver specific genes (adenovirus-5 EIA, SV40 large T antigen mutant).
Utilizing emodin, a tyrosine kinase inhibitor, to repress HER-2/neu function.
Assessing tumor growth suppression and survival prolongation in tumor-bearing mice.
Evaluating the effect of emodin on HER-2/neu-overexpressing human breast cancer cells in vitro and in vivo.

Main Results:

Delivery of therapeutic genes via liposomes or adenovirus vectors suppressed tumor growth and prolonged survival in mice.
Emodin effectively inhibited HER-2/neu tyrosine kinase activity.
Emodin preferentially inhibited the growth of HER-2/neu-overexpressing human breast cancer cells in tissue culture and in nude mice models.

Conclusions:

HER-2/neu is a viable therapeutic target for cancers exhibiting its overexpression.
Gene therapy approaches targeting the HER-2/neu promoter show potential for cancer treatment.
Tyrosine kinase inhibitors like emodin can effectively suppress the growth of HER-2/neu-overexpressing cancers.

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