Personalised medicine has become a mainstay of the pharmaceutical industry. Companion diagnostics, where a specific diagnostic test is performed prior to administration of a drug, is becoming increasingly common. The first companion diagnostic to receive FDA approval was in 1998 and was an immunohistochemistry (IHC) test for the HER2 biomarker linked to the drug Herceptin. HER2 is the receptor that is targeted by Herceptin and, thus, the biological association of the test and drug is clear and unambiguous.
There has been a dramatic increase in the number of drug/diagnostic pairings that have obtained FDA approval. In the last three years alone, a total of nine companion diagnostic tests have been approved, bringing the total to 18 overall. This apparent progress is, however, somewhat misleading, since of the 18 approved diagnostics currently listed on the FDA website, 10 are directed to HER2, either as IHC or in-situ hybridisation (FISH) assays. The remainder are also fairly low complexity tests looking at a single mutation, such as KRAS, and like the HER2 test for Herceptin the biomarker is often the target of the drug.
In recent years it has become clear that the paradigm of the drug target doubling as the biomarker is flawed in many cases. A notable example of this is the case of EGFR inhibitors, such as cetuximab and panitumumab. Here we have seen that the presence of the EGFR receptor is not a strong biomarker and that the mutational status of a different gene in the same pathway, KRAS, is a more important predictor of response. KRAS mutational status is now commonly used as a companion diagnostic for prescribing these drugs, although subsequent studies have shown that KRAS mutational status is not the only determinant of response.
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