Examples of attempts to target downstream of the biomarker of interest, which have met with variable success, have included basket trials testing pan-RAF inhibitors and/or MEK and ERK inhibition in RAS-mutant cancers (Chenard-Poirier et al. 2017; Sullivan et al. 2018, 2020); MEK inhibition in NF1-, GNAQ-, and GNA11-mutant tumors (Wisinski et al. 2023); and mTOR inhibitors for the treatment of TSC1/2-, STK11-, PTEN-, and/or PIK3CA-mutant tumors (NCT02465060, NCT04774952). The gene discussed is PIK3CA; the disease is cancer.