Potential Application of Pharmacogenetics

The promise of pharmacogenetics has been realized for only a few drugs. One reason for the slow pace of development is that much of the science needed to practice gene-based medicine needs to be worked 

While no biopharmaceutical is approved with the requirement of genotyping as a part of its therapeutic indication, a recently approved monoclonal antibody therapy against breast cancer, trastuzumab (Herceptin), is indicated only for those tumors measurably expressing the protein expressed by the gene erbB-2. Because the oncogene product of erbB-2 is elevated 

BOX 14.1. HOW HERCEPTIN NAS APPROVED AS A THERAPY THAT REQUIRES HER2 EXPRESSION TESTS ON PATIENT TUMOR TISSUES BEFORE USE 

By early 1990 Genentech had reported the development of murine monoclonal antibodies with therapeutic potential against tumor cells that overexpress erbB-2. One of these clones was humanized to produce a mouse/human chimeric form termed 4D5 and determined to be a suitable candidate for preclinical and clinical studies [23]. In 1998 the FDA approved the humanized monoclonal antibody, now 

Only 20% to 33% of metastatic breast carcinomas robustly express HER2, and tumors that do not overexpress the protein are unlikely to benefit from treatment. Hence demonstration of clinical benefit in unselected breast cancer patients was a challenging task [24]. The need to keep patients on other chemotherapies added to the complexity of clinical trials. Nevertheless, the decision to first demonstrate overexpression of HER2 antigen levels as one of the key clinical trial inclusion criteria, reached in consultation with the FDA, allowed the investigators to demonstrate efficacy (Table 14.2). 

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