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We will discuss the development of monoclonal antibodies
against the products of the ErbB family oncogenes.
The ErbB family of oncogenes have been implicated in a variety of human cancers,
and the development of monoclonal antibodies against
the ErbB2-Neu onco-protein represented
the first rational targeted therapy against human cancer.
Before we consider how cancer cells are affected my monoclonal antibodies,
we must discuss the differences between cancer cells and normal cells.
Cancer cells have growth independence from growth factors.
That is, growth factors normally are reliant on a variety of signals to keep them alive.
Cancer cells often become independent of this.
In the same way, cancer cells resist cell death on
a situation while normal cells die such as deprivation of nutrients.
Finally, cancer cells can undergo chromosomal alterations
and a stepwise change from less to more malignant cell types.
All of these features,
acquisition of growth independence,
resistance to cell death,
and progressive chromosomal alterations can be affected by
specific targeted disabling of onco-proteins involved in transformation of cells.
A variety of common tumors have abnormalities of the ErbB family of proteins.
Today, we'll concentrate on breast cancer,
a very common tumor in the United States.
Approximately 25-30 percent of breast cancers have abnormalities of
the ErbB2-Neu oncogene and abnormal expression of the ErbB2-Neu onco-protein.
Other common tumors such as lung cancer also have
abnormalities of ErbB oncogenes including the EGF receptor.
This tumor is particularly lethal,
and strategies to disable the EGF receptor may have some significant benefit.