Translating laboratory knowledge into biological therapy and genetic analysis

Genomic instability is one of the earliest features of cancer cell behavior and can lead to gene mutation, amplification, or deletion. Rarely one of these genomic events can give the cell a growth advantage or some other characteristic that contributes to carcinogenesis and also leads to clonal expansion. Solid tumors contain numerous genetic abnormalities and these vary among individuals. New techniques from the laboratory allow unprecedented levels of detail in cancer genetic analysis of human tumors. One technique called comparative genomic hybridization (CGH) can pinpoint areas of the genome that are amplified or deleted. These changes that occur at a high frequency are likely to represent genes that are important in cancer development and progression. How can this be translated into new biologic therapy as well as a better understanding of factors that predict responses to standard chemotherapy to allow better individualized tailoring of treatment? Through the linkage of CGH data on human tumors to their clinical outcomes, specific questions can be asked about the relationship of specific genes to clinical variables. For example, genes that are gained in patients who are resistant to anti-HER-2 antibody (Herceptin) might help select patients for such therapy or identify genes that could be pharmacologically targeted to overcome Herceptin resistance. Prospects for better treatment and recent advances in genomic research may lead to an increased understanding of the basic mechanisms resulting in initiation and progression of breast cancer.