Genetic testing in oncology
While genetic testing can identify patients who will be nonresponsive to certain drug therapies, it can also suggest other drugs as treatment options that might work. These may include pharmaceuticals not usually considered for treatment of a particular cancer.
Editor's note: Scientific information from studies released since this article was written have raised more questions about the Plavix CYP2C19 genome connection as it affects some people. Watch for updates in future issues of Drug Topics.
Recent genomic research has made many advances affecting the use of drug therapy for cancer patients - especially for people with lung, colorectal, and breast cancer. One benchmark finding, reported at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO), discussed evidence that patients with a mutation in the KRAS gene are virtually nonresponsive to the class of drugs termed epidermal growth factor receptor (EGFR) inhibitors.
EGFRs are part of a family of cell receptors known as human epithelial receptors, or HERs, which play an important role in cell metabolism and growth, desirable under normal cell conditions, but not in the case of cancer cells. Oncology drugs such as Vectibix (panitumumab) and Erbitux (cetuximab), typically given for colorectal cancer, are EGFR inhibitors and are designed to target these EGFR receptors and disrupt the metabolic process of cell proliferation. However, the research clearly affirms that these drugs will not work in patients whose genetic tests report the KRAS mutation.
It has been estimated that among all individuals diagnosed with colorectal cancers, between 30% and 40% will have the KRAS mutation, and physicians are now routinely testing their patients before prescribing therapy.
The good news is that while genetic testing can identify patients who will be nonresponsive to certain drug therapies, it can also suggest other drugs as treatment options that might work. These may include pharmaceuticals not usually considered for treatment of a particular cancer.
For example, a patient with colorectal cancer underwent standard-of-care radiation and chemotherapy. After his disease spread to the liver and lungs, a specimen sample from his tumor tissue was sent out for genetic testing. The laboratory reported a striking overexpression of human epidermal growth factor receptor 2 (HER2Nu), and the genetic analysis suggested that the patient might respond to Herceptin (trastuzumab), a drug used to treat breast cancer. The oncologist began Herceptin therapy. A subsequent surgical procedure revealed that where the previous surgeon had placed reference clips to identify liver disease, no cancer was present at all, indicating excellent response to the Herceptin therapy.
Capturing this kind of important genomic outcomes evidence is now the purview of the latest data registries founded by industry, government, and non-profits. They encourage data submissions and provide free public access to researchers, clinicians, and individuals.
See related article in this issue, "Plavix biomarker test can improve patient outcomes."
