Using biomarkers from patients’ tumors in clinical trials may not be as reliable as genetic variation in determining who will benefit most from particular drug treatments. For example, the protein levels detected in a test may differ based the part of a tumor from which a biopsy was obtained and the extent of a cancer’s spread. Protein levels may also differ from one day to the next. Furthermore, depending on the drug company, standards for tests may vary. Some drugs have proven effective in patients who tested negative for the proteins targeted. Therefore, approval of an immunotherapy only for patients with a specific mutation may prevent the therapy from being administered to other patients who might benefit from it. In addition, combining drugs may result in higher efficacy. Pharmaceutical companies are working to develop standard testing for biomarkers as well as new ways to determine which patients will benefit from particular immunotherapies. They are also making efforts to identify “negative biomarkers,” which may indicate patients for whom particular immunotherapies should not be used.